Proteins

Tumor Necrosis Factor-Alpha (TNF-alpha) plays a major role in growth regulation, differentiation, inflammation, viral replication, tumorigenesis, and autoimmune disease. Besides inducing hemorrhagic necrosis of tumors, TNF has been found to be involved in tumorigenesis, tumor metastasis, viral replication, septic shock, fever, inflammation, and autoimmune disease including Crohn’s disease, rheumatoid arthritis and graft-versus-host disease. TNF alpha-1a is a potent lymphoid factor that exerts cytotoxic effects on a wide range of tumor cells and certain other target cells.

Tumor Necrosis Factor-Alpha (TNF-alpha) plays a major role in growth regulation, differentiation, inflammation, viral replication, tumorigenesis, and autoimmune disease. Besides inducing hemorrhagic necrosis of tumors, TNF has been found to be involved in tumorigenesis, tumor metastasis, viral replication, septic shock, fever, inflammation, and autoimmune disease including Crohn’s disease, rheumatoid arthritis and graft-versus-host disease. TNF alpha-1a is a potent lymphoid factor that exerts cytotoxic effects on a wide range of tumor cells and certain other target cells.

Tumor Necrosis Factor-Alpha (TNF-alpha) plays a major role in growth regulation, differentiation, inflammation, viral replication, tumorigenesis, and autoimmune disease. Besides inducing hemorrhagic necrosis of tumors, TNF has been found to be involved in tumorigenesis, tumor metastasis, viral replication, septic shock, fever, inflammation, and autoimmune disease including Crohn’s disease, rheumatoid arthritis and graft-versus-host disease. TNF alpha-1a is a potent lymphoid factor that exerts cytotoxic effects on a wide range of tumor cells and certain other target cells.

Tumor Necrosis Factor-Alpha (TNF-alpha) plays a major role in growth regulation, differentiation, inflammation, viral replication, tumorigenesis, and autoimmune disease. Besides inducing hemorrhagic necrosis of tumors, TNF has been found to be involved in tumorigenesis, tumor metastasis, viral replication, septic shock, fever, inflammation, and autoimmune disease including Crohn’s disease, rheumatoid arthritis and graft-versus-host disease. TNF alpha-1a is a potent lymphoid factor that exerts cytotoxic effects on a wide range of tumor cells and certain other target cells.

Tumor Necrosis Factor-Alpha (TNF-alpha) plays a major role in growth regulation, differentiation, inflammation, viral replication, tumorigenesis, and autoimmune disease. Besides inducing hemorrhagic necrosis of tumors, TNF has been found to be involved in tumorigenesis, tumor metastasis, viral replication, septic shock, fever, inflammation, and autoimmune disease including Crohn’s disease, rheumatoid arthritis and graft-versus-host disease. TNF alpha-1a is a potent lymphoid factor that exerts cytotoxic effects on a wide range of tumor cells and certain other target cells.

TNF is secreted by macrophages, monocytes, neutrophils, T-cells, NK-cells following their stimulation by bacterial LPS. Cells expressing CD4 secrete TNF-alpha while CD8 cells secrete little or no TNF-alpha. The synthesis of TNF-alpha is induced by many different stimuli including interferons, IL2, GM-CSF. TNF-β is a potent mediator of inflammatory and immune responses. It belongs to the TNF family of ligands, and signals through TNFR1 and TNFR2. TNF-β is produced by activated T and B lymphocytes, and has similar activities to TNF-α. It mediates a large variety of inflammatory, immunostimulatory, and antiviral responses.

TNF is secreted by macrophages, monocytes, neutrophils, T-cells, NK-cells following their stimulation by bacterial LPS. Cells expressing CD4 secrete TNF-alpha while CD8 cells secrete little or no TNF-alpha. The synthesis of TNF-alpha is induced by many different stimuli including interferons, IL2, GM-CSF. TNF-β is a potent mediator of inflammatory and immune responses. It belongs to the TNF family of ligands, and signals through TNFR1 and TNFR2. TNF-β is produced by activated T and B lymphocytes, and has similar activities to TNF-α. It mediates a large variety of inflammatory, immunostimulatory, and antiviral responses.

TNF is secreted by macrophages, monocytes, neutrophils, T-cells, NK-cells following their stimulation by bacterial LPS. Cells expressing CD4 secrete TNF-alpha while CD8 cells secrete little or no TNF-alpha. The synthesis of TNF-alpha is induced by many different stimuli including interferons, IL2, GM-CSF. TNF-β is a potent mediator of inflammatory and immune responses. It belongs to the TNF family of ligands, and signals through TNFR1 and TNFR2. TNF-β is produced by activated T and B lymphocytes, and has similar activities to TNF-α. It mediates a large variety of inflammatory, immunostimulatory, and antiviral responses.

Thrombopoietin (TPO) is a glycoprotein hormone which belongs to the EPO/TPO family. It produced by the liver and kidney which regulates the production of platelets. TPO stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets. Lineage-specific cytokine affects the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.

Thrombopoietin (TPO) is a glycoprotein hormone which belongs to the EPO/TPO family. It produced by the liver and kidney which regulates the production of platelets. TPO stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets. Lineage-specific cytokine affects the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.

Thrombopoietin (TPO) is a glycoprotein hormone which belongs to the EPO/TPO family. It produced by the liver and kidney which regulates the production of platelets. TPO stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets. Lineage-specific cytokine affects the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.

Thrombopoietin (TPO) is a glycoprotein hormone which belongs to the EPO/TPO family. It produced by the liver and kidney which regulates the production of platelets. TPO stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets. Lineage-specific cytokine affects the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.

Thrombopoietin (TPO), also known as C-mpl ligand, MGDF and Thpo, is a glycoprotein hormone belonging to the EPO/TPO family. It is expressed mainly in the liver, kidney and skeletal muscle. TPO binds and signals through MLP/C_MPL receptor. It stimulates the proliferation and maturation of megakaryocytes from their committed progenitor cells, and it regulates the production and circulation of platelets. TPO has also been reported to promote the apoptosis of hypoxia-sensitized neurons and to inhibit neuronal differentiation.

Thrombopoietin (TPO), also known as C-mpl ligand, MGDF and Thpo, is a glycoprotein hormone belonging to the EPO/TPO family. It is expressed mainly in the liver, kidney and skeletal muscle. TPO binds and signals through MLP/C_MPL receptor. It stimulates the proliferation and maturation of megakaryocytes from their committed progenitor cells, and it regulates the production and circulation of platelets. TPO has also been reported to promote the apoptosis of hypoxia-sensitized neurons and to inhibit neuronal differentiation.

Thrombopoietin (TPO), also known as C-mpl ligand, MGDF and Thpo, is a glycoprotein hormone belonging to the EPO/TPO family. It is expressed mainly in the liver, kidney and skeletal muscle. TPO binds and signals through MLP/C_MPL receptor. It stimulates the proliferation and maturation of megakaryocytes from their committed progenitor cells, and it regulates the production and circulation of platelets. TPO has also been reported to promote the apoptosis of hypoxia-sensitized neurons and to inhibit neuronal differentiation.

TNF-related apoptosis-inducing ligand (TRAIL), also known as Tumor Necrosis Factor Super-Family 10 (TNFSF10) or apoptosis 2 ligand (Apo2L), is a pleiotropic cytokine thatbelongs to the TNF superfamily. Full length TRAIL expressed in vivo is a type II transmembrane protein, although the soluble form also exists and functions. TRAIL has four major receptors: two death receptors DR4 and DR5, and two decoy receptors DcR1 and DcR2. TRAIL binds to the death receptors which recruits the FAS-associated death domain and activates caspases 8 and 10 which eventually leads to apoptosis. Because of its antitumor potential, TRAIL is activelystudied as a therapeutic agent. On the other hand, abnormal expression of TRAIL in small arteries can induce the proliferation of smooth muscle cells, thereby increasing vascular remodeling and pulmonary arterial hypertension.

TNF-related apoptosis-inducing ligand (TRAIL), also known as Tumor Necrosis Factor Super-Family 10 (TNFSF10) or apoptosis 2 ligand (Apo2L), is a pleiotropic cytokine thatbelongs to the TNF superfamily. Full length TRAIL expressed in vivo is a type II transmembrane protein, although the soluble form also exists and functions. TRAIL has four major receptors: two death receptors DR4 and DR5, and two decoy receptors DcR1 and DcR2. TRAIL binds to the death receptors which recruits the FAS-associated death domain and activates caspases 8 and 10 which eventually leads to apoptosis. Because of its antitumor potential, TRAIL is activelystudied as a therapeutic agent. On the other hand, abnormal expression of TRAIL in small arteries can induce the proliferation of smooth muscle cells, thereby increasing vascular remodeling and pulmonary arterial hypertension.

TNF-related apoptosis-inducing ligand (TRAIL), also known as Tumor Necrosis Factor Super-Family 10 (TNFSF10) or apoptosis 2 ligand (Apo2L), is a pleiotropic cytokine thatbelongs to the TNF superfamily. Full length TRAIL expressed in vivo is a type II transmembrane protein, although the soluble form also exists and functions. TRAIL has four major receptors: two death receptors DR4 and DR5, and two decoy receptors DcR1 and DcR2. TRAIL binds to the death receptors which recruits the FAS-associated death domain and activates caspases 8 and 10 which eventually leads to apoptosis. Because of its antitumor potential, TRAIL is activelystudied as a therapeutic agent. On the other hand, abnormal expression of TRAIL in small arteries can induce the proliferation of smooth muscle cells, thereby increasing vascular remodeling and pulmonary arterial hypertension.

TRAIL/Apo2L, also known as Tumor Necrosis Factor Super-Family 10 (TNFSF10), is a pleiotropic cytokine thatbelongs to the TNF superfamily. The full length TRAIL expressed in vivo is a Type II transmembrane protein, although the soluble form also exists and functions. TRAIL has four major receptors: two death receptors DR4 and DR5, two decoy receptors DcR1 and DcR2. TRAIL binds to the death receptors, recruits the FAS-associated death domain, activates caspases 8 and 10, and eventually leads to apoptosis. Because of its antitumor potential, TRAIL is actively studied as a therapeutic agent. On the other hand, abnormal expression of TRAIL in small arteries can induce the proliferation of smooth muscle cells, resulting in increasing vascular remodeling and pulmonary arterial hypertension.

TRAIL/Apo2L, also known as Tumor Necrosis Factor Super-Family 10 (TNFSF10), is a pleiotropic cytokine thatbelongs to the TNF superfamily. The full length TRAIL expressed in vivo is a Type II transmembrane protein, although the soluble form also exists and functions. TRAIL has four major receptors: two death receptors DR4 and DR5, two decoy receptors DcR1 and DcR2. TRAIL binds to the death receptors, recruits the FAS-associated death domain, activates caspases 8 and 10, and eventually leads to apoptosis. Because of its antitumor potential, TRAIL is actively studied as a therapeutic agent. On the other hand, abnormal expression of TRAIL in small arteries can induce the proliferation of smooth muscle cells, resulting in increasing vascular remodeling and pulmonary arterial hypertension.

TRAIL/Apo2L, also known as Tumor Necrosis Factor Super-Family 10 (TNFSF10), is a pleiotropic cytokine thatbelongs to the TNF superfamily. The full length TRAIL expressed in vivo is a Type II transmembrane protein, although the soluble form also exists and functions. TRAIL has four major receptors: two death receptors DR4 and DR5, two decoy receptors DcR1 and DcR2. TRAIL binds to the death receptors, recruits the FAS-associated death domain, activates caspases 8 and 10, and eventually leads to apoptosis. Because of its antitumor potential, TRAIL is actively studied as a therapeutic agent. On the other hand, abnormal expression of TRAIL in small arteries can induce the proliferation of smooth muscle cells, resulting in increasing vascular remodeling and pulmonary arterial hypertension.

Tyrosine kinase receptor A (Trk-A) is a member of the neurotrophic tyrosine kinase receptor family which includes three members: Trk-A, Trk-B and Trk-C. Trk-A is involved in the development and maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic neurons.

Tyrosine kinase receptor A (Trk-A) is a member of the neurotrophic tyrosine kinase receptor family which includes three members: Trk-A, Trk-B and Trk-C. Trk-A is involved in the development and maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic neurons.

Tyrosine kinase receptor A (Trk-A) is a member of the neurotrophic tyrosine kinase receptor family which includes three members: Trk-A, Trk-B and Trk-C. Trk-A is involved in the development and maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic neurons.

TSLP is a hemopoietic protein that is expressed in the heart, liver and prostate. TSLP overlaps biological activities with IL-7 and binds with the heterodimeric receptor complex consisting of the IL-7R alpha chain (IL-7Rα) and the TSLP-specific chain (TSLPR). Like IL-7, TSLP induces phosphorylation of STAT3 and STAT5, but uses kinases other than the JAKs for activation. TSLP prohibited apoptosis and stimulated growth of the human acute myeloid leukemia (AML)-derived cell line MUTZ3. It induces the release of T cell-attracting chemokines TARC and MDC from monocytes and activates CD11c(+) dendritic cells (DCs). TSLP activated DCs primed naive T cells to produce the proallergic cytokines (IL-4, IL-5, IL-13, TNFα) while down-regulating IL-10 and IFN-γ suggesting a role in initiating allergic inflammation.

TSLP is a hemopoietic protein that is expressed in the heart, liver and prostate. TSLP overlaps biological activities with IL-7 and binds with the heterodimeric receptor complex consisting of the IL-7R alpha chain (IL-7Rα) and the TSLP-specific chain (TSLPR). Like IL-7, TSLP induces phosphorylation of STAT3 and STAT5, but uses kinases other than the JAKs for activation. TSLP prohibited apoptosis and stimulated growth of the human acute myeloid leukemia (AML)-derived cell line MUTZ3. It induces the release of T cell-attracting chemokines TARC and MDC from monocytes and activates CD11c(+) dendritic cells (DCs). TSLP activated DCs primed naive T cells to produce the proallergic cytokines (IL-4, IL-5, IL-13, TNFα) while down-regulating IL-10 and IFN-γ suggesting a role in initiating allergic inflammation.

TWEAK, short for TNF-related weak inducer of apoptosis, is also known as TNFSF12 and DR3LG. It is a type II transmembrane protein belonging to the TNF superfamily. It is expressed widely in many tissues, such as the heart, skeletal muscle, spleen and peripheral blood. Binding of TWEAK to its receptor TWEAKR induces NF-κB activation, chemokine secretion and apoptosis in certain cell types. TWEAK has also been reported to promote endothelial cell proliferation and migration, thus serving as a regulator of angiogenesis.

TWEAK, short for TNF-related weak inducer of apoptosis, is also known as TNFSF12 and DR3LG. It is a type II transmembrane protein belonging to the TNF superfamily. It is expressed widely in many tissues, such as the heart, skeletal muscle, spleen and peripheral blood. Binding of TWEAK to its receptor TWEAKR induces NF-κB activation, chemokine secretion and apoptosis in certain cell types. TWEAK has also been reported to promote endothelial cell proliferation and migration, thus serving as a regulator of angiogenesis.

TWEAK, short for TNF-related weak inducer of apoptosis, is also known as TNFSF12 and DR3LG. It is a type II transmembrane protein belonging to the TNF superfamily. It is expressed widely in many tissues, such as the heart, skeletal muscle, spleen and peripheral blood. Binding of TWEAK to its receptor TWEAKR induces NF-κB activation, chemokine secretion and apoptosis in certain cell types. TWEAK has also been reported to promote endothelial cell proliferation and migration, thus serving as a regulator of angiogenesis.

Vascular Endothelial Growth Factor (VEGF) was initially purified from media conditioned by normal bovine pituitary folliculo-stellate cells and by a variety of transformed cell lines as a mitogen specific for vascular endothelial cells. It was subsequently found to be identical to an independently discovered vascular permeability factor (VPF), which was previously identified in media conditioned by tumor cell lines based on its ability to increase the permeability of capillary blood vessels. Three mouse cDNA clones, which arise through alternative splicing and which encode mature mouse monomeric VEGF having 120, 164, or 188, amino acids, respectively, have been identified. Two receptor tyrosine kinases (RTKs), Flt-1 and Flk-1 (the mouse homologue of human KDR), both members of the type III subclass of RTKs containing seven immunoglobulin-like repeats in their extracellular domains, have been shown to bind VEGF with high affinity. The roles of the homodimers of KDR, Flt, and the heterodimer of KDR/Flt in VEGF signal transduction remain to be elucidated. In vivo, VEGF has been found to be a potent angiogenesis inducer.

Vascular Endothelial Growth Factor (VEGF) was initially purified from media conditioned by normal bovine pituitary folliculo-stellate cells and by a variety of transformed cell lines as a mitogen specific for vascular endothelial cells. It was subsequently found to be identical to an independently discovered vascular permeability factor (VPF), which was previously identified in media conditioned by tumor cell lines based on its ability to increase the permeability of capillary blood vessels. Three mouse cDNA clones, which arise through alternative splicing and which encode mature mouse monomeric VEGF having 120, 164, or 188, amino acids, respectively, have been identified. Two receptor tyrosine kinases (RTKs), Flt-1 and Flk-1 (the mouse homologue of human KDR), both members of the type III subclass of RTKs containing seven immunoglobulin-like repeats in their extracellular domains, have been shown to bind VEGF with high affinity. The roles of the homodimers of KDR, Flt, and the heterodimer of KDR/Flt in VEGF signal transduction remain to be elucidated. In vivo, VEGF has been found to be a potent angiogenesis inducer.

Vascular Endothelial Growth Factor (VEGF) was initially purified from media conditioned by normal bovine pituitary folliculo-stellate cells and by a variety of transformed cell lines as a mitogen specific for vascular endothelial cells. It was subsequently found to be identical to an independently discovered vascular permeability factor (VPF), which was previously identified in media conditioned by tumor cell lines based on its ability to increase the permeability of capillary blood vessels. Three mouse cDNA clones, which arise through alternative splicing and which encode mature mouse monomeric VEGF having 120, 164, or 188, amino acids, respectively, have been identified. Two receptor tyrosine kinases (RTKs), Flt-1 and Flk-1 (the mouse homologue of human KDR), both members of the type III subclass of RTKs containing seven immunoglobulin-like repeats in their extracellular domains, have been shown to bind VEGF with high affinity. The roles of the homodimers of KDR, Flt, and the heterodimer of KDR/Flt in VEGF signal transduction remain to be elucidated. In vivo, VEGF has been found to be a potent angiogenesis inducer.

Vascular endothelial growth factor C (VEGF-C) is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family, is active in angiogenesis, lymphangiogenesis and endothelial cell growth and survival, and can also affect the permeability of blood vessels. VEGF-C is expressed in various tissues, however it is not produced in peripheral blood lymphocytes. It forms cell surface-associated non-covalent disulfide linked homodimers, and can bind and activate both VEGFR-2 (flk1) and VEGFR-3 (flt4) receptors. The structure and function of VEGF-C is similar to those of vascular endothelial growth factor D (VEGF-D).

Vascular endothelial growth factor C (VEGF-C) is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family, is active in angiogenesis, lymphangiogenesis and endothelial cell growth and survival, and can also affect the permeability of blood vessels. VEGF-C is expressed in various tissues, however it is not produced in peripheral blood lymphocytes. It forms cell surface-associated non-covalent disulfide linked homodimers, and can bind and activate both VEGFR-2 (flk1) and VEGFR-3 (flt4) receptors. The structure and function of VEGF-C is similar to those of vascular endothelial growth factor D (VEGF-D).

Vascular endothelial growth factor C (VEGF-C) is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family, is active in angiogenesis, lymphangiogenesis and endothelial cell growth and survival, and can also affect the permeability of blood vessels. VEGF-C is expressed in various tissues, however it is not produced in peripheral blood lymphocytes. It forms cell surface-associated non-covalent disulfide linked homodimers, and can bind and activate both VEGFR-2 (flk1) and VEGFR-3 (flt4) receptors. The structure and function of VEGF-C is similar to those of vascular endothelial growth factor D (VEGF-D).

Vascular Endothelial Growth Factor (VEGF)-D, also known as c-Fos-induced growth factor (FIGF), is a member of the PDGF/VEGF growth factor family. It is expressed highly in lung, heart and small intestine, and at lower levels in skeletal muscle, colon and pancreas. It binds to VEGFR-2 and VEGFR-3 receptors and activates downstream signals. VEGF-D is a growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth. It is involved in many developmental and physiological processes including the formation of venous and lymphatic vascular systems during embryogenesis and the maintenance of differentiated lymphatic endothelium in adults. In tumor pathology, it has been reported to play a role in restructuring of lymphatic channels and regional lymph node metastasis.

Vascular Endothelial Growth Factor (VEGF)-D, also known as c-Fos-induced growth factor (FIGF), is a member of the PDGF/VEGF growth factor family. It is expressed highly in lung, heart and small intestine, and at lower levels in skeletal muscle, colon and pancreas. It binds to VEGFR-2 and VEGFR-3 receptors and activates downstream signals. VEGF-D is a growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth. It is involved in many developmental and physiological processes including the formation of venous and lymphatic vascular systems during embryogenesis and the maintenance of differentiated lymphatic endothelium in adults. In tumor pathology, it has been reported to play a role in restructuring of lymphatic channels and regional lymph node metastasis.

Vascular Endothelial Growth Factor (VEGF)-D, also known as c-Fos-induced growth factor (FIGF), is a member of the PDGF/VEGF growth factor family. It is expressed highly in lung, heart and small intestine, and at lower levels in skeletal muscle, colon and pancreas. It binds to VEGFR-2 and VEGFR-3 receptors and activates downstream signals. VEGF-D is a growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth. It is involved in many developmental and physiological processes including the formation of venous and lymphatic vascular systems during embryogenesis and the maintenance of differentiated lymphatic endothelium in adults. In tumor pathology, it has been reported to play a role in restructuring of lymphatic channels and regional lymph node metastasis.

VEGF-R2 belongs to a family of proteins called receptor tyrosine kinases. The receptor has three main parts: one part extends out of the cell and binds to VEGF, another spans the cell’s membrane, while the third part is found inside the cell. The current model of VEGF-R2 activation is that VEGF binds to individual VEGF-R2 receptor proteins on the membrane, and brings two of them close enough to form a complex called a dimer. The receptor dimer is activated and initiates signaling within the cell. VEGF-R2 is a receptor tyrosine kinase (RTK) which transduces biochemical signals via lateral dimerization in the plasma membrane. Like most RTKs, VEGF-R2 is composed of an extracellular (EC) domain, a transmembrane (TM) domain, and an intracellular (IC) domain consisting of a kinase domain and sequences required for downstream signaling. The EC domain consists of seven immunoglobulin homology (Ig) domains, termed D1 (at the N-terminus) to D7 (closest to the membrane). VEGF-R2 binds to, and is activated by the ligands VEGF-A, VEGF-E, and a number of processed forms of VEGF-C and VEGF-D. Ligand binding to VEGF-R2 is mediated by Ig-domains 2 and 3 and the linker between D2 and D3.

VEGF-R2 belongs to a family of proteins called receptor tyrosine kinases. The receptor has three main parts: one part extends out of the cell and binds to VEGF, another spans the cell’s membrane, while the third part is found inside the cell. The current model of VEGF-R2 activation is that VEGF binds to individual VEGF-R2 receptor proteins on the membrane, and brings two of them close enough to form a complex called a dimer. The receptor dimer is activated and initiates signaling within the cell. VEGF-R2 is a receptor tyrosine kinase (RTK) which transduces biochemical signals via lateral dimerization in the plasma membrane. Like most RTKs, VEGF-R2 is composed of an extracellular (EC) domain, a transmembrane (TM) domain, and an intracellular (IC) domain consisting of a kinase domain and sequences required for downstream signaling. The EC domain consists of seven immunoglobulin homology (Ig) domains, termed D1 (at the N-terminus) to D7 (closest to the membrane). VEGF-R2 binds to, and is activated by the ligands VEGF-A, VEGF-E, and a number of processed forms of VEGF-C and VEGF-D. Ligand binding to VEGF-R2 is mediated by Ig-domains 2 and 3 and the linker between D2 and D3.

VEGF-R2 belongs to a family of proteins called receptor tyrosine kinases. The receptor has three main parts: one part extends out of the cell and binds to VEGF, another spans the cell’s membrane, while the third part is found inside the cell. The current model of VEGF-R2 activation is that VEGF binds to individual VEGF-R2 receptor proteins on the membrane, and brings two of them close enough to form a complex called a dimer. The receptor dimer is activated and initiates signaling within the cell. VEGF-R2 is a receptor tyrosine kinase (RTK) which transduces biochemical signals via lateral dimerization in the plasma membrane. Like most RTKs, VEGF-R2 is composed of an extracellular (EC) domain, a transmembrane (TM) domain, and an intracellular (IC) domain consisting of a kinase domain and sequences required for downstream signaling. The EC domain consists of seven immunoglobulin homology (Ig) domains, termed D1 (at the N-terminus) to D7 (closest to the membrane). VEGF-R2 binds to, and is activated by the ligands VEGF-A, VEGF-E, and a number of processed forms of VEGF-C and VEGF-D. Ligand binding to VEGF-R2 is mediated by Ig-domains 2 and 3 and the linker between D2 and D3.

VEGF was initially purified from media conditioned by normal bovine pituitary folliculo-stellate cells and by a variety of transformed cell lines as a mitogen specific for vascular endothelial cells. It was subsequently found to be identical to an independently discovered vascular permeability factor (VPF), which was previously identified in media conditioned by tumor cell lines based on its ability to increase the permeability of capillary blood vessels. Three mouse cDNA clones, which arise through alternative splicing and which encode mature mouse monomeric VEGF having 120, 164, or 188, amino acids, respectively, have been identified. Two receptor tyrosine kinases (RTKs), Flt-1 and Flk-1 (the mouse homologue of human KDR), both members of the type III subclass of RTKs containing seven immunoglobulin-like repeats in their extracellular domains, have been shown to bind VEGF with high affinity. The roles of the homodimers of KDR, Flt, and the heterodimer ofKDR/Flt in VEGF signal transduction remain to be elucidated.In vivo, VEGF has been found to be a potent angiogenesis inducer.

VEGF was initially purified from media conditioned by normal bovine pituitary folliculo-stellate cells and by a variety of transformed cell lines as a mitogen specific for vascular endothelial cells. It was subsequently found to be identical to an independently discovered vascular permeability factor (VPF), which was previously identified in media conditioned by tumor cell lines based on its ability to increase the permeability of capillary blood vessels. Three mouse cDNA clones, which arise through alternative splicing and which encode mature mouse monomeric VEGF having 120, 164, or 188, amino acids, respectively, have been identified. Two receptor tyrosine kinases (RTKs), Flt-1 and Flk-1 (the mouse homologue of human KDR), both members of the type III subclass of RTKs containing seven immunoglobulin-like repeats in their extracellular domains, have been shown to bind VEGF with high affinity. The roles of the homodimers of KDR, Flt, and the heterodimer ofKDR/Flt in VEGF signal transduction remain to be elucidated.In vivo, VEGF has been found to be a potent angiogenesis inducer.

VEGF-A121 is one of five isoforms (121, 145, 165, 189, and 206) of VEGF protein, a cytokine belonging to the Platelet Differentiation Growth Factor (PDGF) family, and existing as a disulfide-linked homodimeric glycoprotein. In contrast to the longer isoforms, VEGF-A121 is more freely diffusible, and cannot bind to heparin. In vivo, VEGF is expressed predominantly in lung, heart, kidney, and adrenal glands, and the expression of VEGF is up-regulated by a number of growth factors, including PDGF, Fibroblast Growth Factor (FGF), Epidermal Growth Factor (EGF), and Tumor Necrosis Factor (TNF). VEGF signals via binding to two tyrosine kinase receptors: the Fms-like tyrosine kinase 1 (Flt-1) and the kinase domain receptor (KDR). VEGF is a specific mitogen and survival factor, contributing to abnormal angiogenesis and cancer development.

VEGF-A121 is one of five isoforms (121, 145, 165, 189, and 206) of VEGF protein, a cytokine belonging to the Platelet Differentiation Growth Factor (PDGF) family, and existing as a disulfide-linked homodimeric glycoprotein. In contrast to the longer isoforms, VEGF-A121 is more freely diffusible, and cannot bind to heparin. In vivo, VEGF is expressed predominantly in lung, heart, kidney, and adrenal glands, and the expression of VEGF is up-regulated by a number of growth factors, including PDGF, Fibroblast Growth Factor (FGF), Epidermal Growth Factor (EGF), and Tumor Necrosis Factor (TNF). VEGF signals via binding to two tyrosine kinase receptors: the Fms-like tyrosine kinase 1 (Flt-1) and the kinase domain receptor (KDR). VEGF is a specific mitogen and survival factor, contributing to abnormal angiogenesis and cancer development.

Vascular Endothelial Growth Factor (VEGF) was initially purified from media conditioned by normal bovine pituitary folliculo-stellate cells and by a variety of transformed cell lines as a mitogen specific for vascular endothelial cells. It was subsequently found to be identical to an independently discovered vascular permeability factor (VPF), which was previously identified in media conditioned by tumor cell lines based on its ability to increase the permeability of capillary blood vessels. Three mouse cDNA clones, which arise through alternative splicing and which encode mature mouse monomeric VEGF having 120, 164, or 188, amino acids, respectively, have been identified. Two receptor tyrosine kinases (RTKs), Flt-1 and Flk-1 (the mouse homologue of human KDR), both members of the type III subclass of RTKs containing seven immunoglobulin-like repeats in their extracellular domains, have been shown to bind VEGF with high affinity. The roles of the homodimers of KDR, Flt, and the heterodimer of KDR/Flt in VEGF signal transduction remain to be elucidated. In vivo, VEGF has been found to be a potent angiogenesis inducer.

Vascular Endothelial Growth Factor (VEGF) was initially purified from media conditioned by normal bovine pituitary folliculo-stellate cells and by a variety of transformed cell lines as a mitogen specific for vascular endothelial cells. It was subsequently found to be identical to an independently discovered vascular permeability factor (VPF), which was previously identified in media conditioned by tumor cell lines based on its ability to increase the permeability of capillary blood vessels. Three mouse cDNA clones, which arise through alternative splicing and which encode mature mouse monomeric VEGF having 120, 164, or 188, amino acids, respectively, have been identified. Two receptor tyrosine kinases (RTKs), Flt-1 and Flk-1 (the mouse homologue of human KDR), both members of the type III subclass of RTKs containing seven immunoglobulin-like repeats in their extracellular domains, have been shown to bind VEGF with high affinity. The roles of the homodimers of KDR, Flt, and the heterodimer of KDR/Flt in VEGF signal transduction remain to be elucidated. In vivo, VEGF has been found to be a potent angiogenesis inducer.

Vascular Endothelial Growth Factor A164 (VEGF-A164), a member of the cysteine knot growth factor, is one of major isoforms of VEGF-As. VEGF-As are endothelial cell-specific mitogens with angiogenic and vascular permeability-inducing properties. During maturation, rat VEGF-A is alternatively spliced to generate rVEGF-A120, rVEGF-A164 and rVEGF-A188 which correspond to hVEGF-A121, hVEGF-A165 and hVEGF-A189 in human, respectively (the numbers designate the amino acid residues). The active form of rVEGF-A164 is either a homodimeric or heterodimeric polypeptides which bind to the transmembrane tyrosine kinases receptors FLT1, FLK1 or KDR or to the non-tyrosine kinase neuropilin receptors NRP1/2.

Vascular Endothelial Growth Factor A164 (VEGF-A164), a member of the cysteine knot growth factor, is one of major isoforms of VEGF-As. VEGF-As are endothelial cell-specific mitogens with angiogenic and vascular permeability-inducing properties. During maturation, rat VEGF-A is alternatively spliced to generate rVEGF-A120, rVEGF-A164 and rVEGF-A188 which correspond to hVEGF-A121, hVEGF-A165 and hVEGF-A189 in human, respectively (the numbers designate the amino acid residues). The active form of rVEGF-A164 is either a homodimeric or heterodimeric polypeptides which bind to the transmembrane tyrosine kinases receptors FLT1, FLK1 or KDR or to the non-tyrosine kinase neuropilin receptors NRP1/2.

Vascular Endothelial Growth Factor A164 (VEGF-A164), a member of the cysteine knot growth factor, is one of major isoforms of VEGF-As. VEGF-As are endothelial cell-specific mitogens with angiogenic and vascular permeability-inducing properties. During maturation, rat VEGF-A is alternatively spliced to generate rVEGF-A120, rVEGF-A164 and rVEGF-A188 which correspond to hVEGF-A121, hVEGF-A165 and hVEGF-A189 in human, respectively (the numbers designate the amino acid residues). The active form of rVEGF-A164 is either a homodimeric or heterodimeric polypeptides which bind to the transmembrane tyrosine kinases receptors FLT1, FLK1 or KDR or to the non-tyrosine kinase neuropilin receptors NRP1/2.