cd05054: PTKc_VEGFR (this model, PSSM-Id:173635 is obsolete and has been replaced by 270647)
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors
Protein Tyrosine Kinase (PTK) family; Vascular Endothelial Growth Factor Receptor (VEGFR) subfamily; catalytic (c) domain. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. VEGFR1 binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow.
Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structures of human VEGFR2 bound to an aryl-oxazole inhibitor and other inhibitors.