Tyrosine-protein kinase, vascular endothelial growth factor receptor 2 (VEGFR2)
InterPro Protein Domain record
-
description
-
-
<p>Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [<cite idref="PUB00005115"/>]:</p><p> <ul> <li>Serine/threonine-protein kinases</li><li>Tyrosine-protein kinases</li><li>Dual specific protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)</li> </ul> </p><p>Protein kinase function has been evolutionarily conserved from <taxon tax_id="562">Escherichia coli</taxon> to human [<cite idref="PUB00020114"/>]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [<cite idref="PUB00015362"/>]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [<cite idref="PUB00034898"/>], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [<cite idref="PUB00034899"/>].</p><p>Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups [<cite idref="PUB00020114"/>]:</p><p> <ul> <li>Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis [<cite idref="PUB00052410"/>]. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction [<cite idref="PUB00052411"/>]. </li> </ul> </p><p> <ul> <li>Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [<cite idref="PUB00052412"/>].</li> </ul> </p><p>Vascular endothelial growth factor (VEGF) is a potent and specific endothelial cell mitogen that regulates blood and lymphatic vessel development and homeostasis [<cite idref="PUB00013873"/>, <cite idref="PUB00013875"/>]. EGFs are predominantly produced by endothelial, hematopoietic, and stromal cells in response to hypoxia and upon stimulation by growth factors such as transforming growth factor beta (TGFbeta), interleukins, or platelet-derived growth factors [<cite idref="PUB00052418"/>]. VEGFs specifically interact with one or several receptor tyrosine kinases, VEGF receptors, and with distinct co-receptors such as neuropilins or heparan sulphate glycosaminoglycans. The VEGF receptor family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4) [<cite idref="PUB00013877"/>]. Among these receptors, VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly, and VEGFR-3 shows essentially no binding, although it does bind to other members of the VEGF family. VEGF receptors have a characteristic structure, with 7 Ig-like domains in the extracellular domain and a cytoplasmic tyrosine kinase domain with a long kinase insert region. VEGF receptors are activated upon ligand-mediated dimerisation.</p><p>This entry represents VEGFR-2 proteins. The tyrosine kinase domain of VEGFR-2 tranduces signals for endothelial cells with a greater efficacy than VEGFR-1. VEGFR-2 expression in adult endothelial cells appears to account for most of the mitogenic and chemotactic effects of VEGF [<cite idref="PUB00013878"/>]. At the post-receptor level, activation of endothelial cells by VEGF leads to the autophosphorylation of VEGFR-2 and the subsequent tyrosine phosphorylation of numerous downstream targets.</p>
-
label
-
-
Tyrosine-protein kinase, vascular endothelial growth factor receptor 2 (VEGFR2)
-
attributionURL
-
-
signatures_SMART
-
-
type
-
-
seeAlso
-
-
children
-
-
contains
-
-
PDB_structure
-