DegronMD - P09619(PDGFRB)

FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11331881, ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1396585, ECO:0000269|PubMed:1653029, ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:1846866, ECO:0000269|PubMed:20494825, ECO:0000269|PubMed:20529858, ECO:0000269|PubMed:21098708, ECO:0000269|PubMed:21679854, ECO:0000269|PubMed:21733313, ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:26599395, ECO:0000269|PubMed:2835772, ECO:0000269|PubMed:2850496, ECO:0000269|PubMed:7685273, ECO:0000269|PubMed:7691811, ECO:0000269|PubMed:7692233, ECO:0000269|PubMed:8195171}. View more >>

GO - Biological processes (BP): aging [GO:0007568]; angiogenesis [GO:0001525]; aorta morphogenesis [GO:0035909]; cardiac myofibril assembly [GO:0055003]; cell chemotaxis [GO:0060326]; cell migration [GO:0016477]; cell migration involved in coronary angiogenesis [GO:0060981]; cell migration involved in vasculogenesis [GO:0035441]; glycosaminoglycan biosynthetic process [GO:0006024]; inner ear development [GO:0048839]; lung growth [GO:0060437]; male gonad development [GO:0008584]; metanephric comma-shaped body morphogenesis [GO:0072278]; metanephric glomerular capillary formation [GO:0072277]; metanephric glomerular mesangial cell proliferation involved in metanephros development [GO:0072262]; metanephric mesenchymal cell migration [GO:0035789]; metanephric mesenchyme development [GO:0072075]; metanephric S-shaped body morphogenesis [GO:0072284]; negative regulation of apoptotic process [GO:0043066]; peptidyl-tyrosine phosphorylation [GO:0018108]; phosphatidylinositol-mediated signaling [GO:0048015]; phosphatidylinositol metabolic process [GO:0046488]; platelet-derived growth factor receptor-beta signaling pathway [GO:0035791]; platelet-derived growth factor receptor signaling pathway [GO:0048008]; positive regulation of apoptotic process [GO:0043065]; positive regulation of calcium ion import [GO:0090280]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway [GO:0038091]; positive regulation of chemotaxis [GO:0050921]; positive regulation of collagen biosynthetic process [GO:0032967]; positive regulation of DNA biosynthetic process [GO:2000573]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of hepatic stellate cell activation [GO:2000491]; positive regulation of kinase activity [GO:0033674]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway [GO:0035793]; positive regulation of mitotic nuclear division [GO:0045840]; positive regulation of phosphatidylinositol 3-kinase activity [GO:0043552]; positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068]; positive regulation of phospholipase C activity [GO:0010863]; positive regulation of phosphoprotein phosphatase activity [GO:0032516]; positive regulation of reactive oxygen species metabolic process [GO:2000379]; positive regulation of Rho protein signal transduction [GO:0035025]; positive regulation of smooth muscle cell migration [GO:0014911]; positive regulation of smooth muscle cell proliferation [GO:0048661]; protein autophosphorylation [GO:0046777]; regulation of actin cytoskeleton organization [GO:0032956]; response to estradiol [GO:0032355]; response to estrogen [GO:0043627]; response to fluid shear stress [GO:0034405]; response to hydrogen peroxide [GO:0042542]; response to hyperoxia [GO:0055093]; response to retinoic acid [GO:0032526]; response to toxic substance [GO:0009636]; retina vasculature development in camera-type eye [GO:0061298]; signal transduction [GO:0007165]; smooth muscle cell chemotaxis [GO:0071670]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]; wound healing [GO:0042060] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S1055T	TCGA-AD-6889	COAD	TCGA	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation altering degron motif	0.6005
p.S1055T	DO8463	COAD	ICGC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation altering degron motif	0.6005
p.A1045D	TCGA-CN-6021	HNSC	TCGA	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.1389
p.A1045D	DO15847	HNSC	ICGC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.1389
p.P1042S	TCGA-EE-A182	SKCM	TCGA	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.0556
p.P1042S	TCGA-ER-A19M	SKCM	TCGA	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.0556
p.P1042S	DO37814	SKCM	ICGC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.0556
p.P1042S	DO37798	SKCM	ICGC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.0556
p.P1042L	TCGA-ER-A19M	SKCM	TCGA	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.0556
p.P1042L	DO37798	SKCM	ICGC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.0556
p.S1043R	DO229006	LICA	ICGC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.0833
p.T1057N	DO228887	LICA	ICGC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.3056
p.T1057P	SIDM00529	Breast Carcinoma	GDSC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.3056
p.T1057P	ACH-000621	Breast Cancer	CCLE	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.3056
p.T1057P	MDA-MB-157	breast	COSMIC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.3056
p.E1051Q	SIDM00133	Non-Small Cell Lung Carcinoma	GDSC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.3056
p.E1051Q	ACH-000861	Lung Cancer	CCLE	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.3056
p.E1051Q	HOP-62	lung	COSMIC	VNTSS	DEG_SPOP_SBC_1	1052:1056	Mutation rewiring degron network	0.3056

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PDGFRB

UniProt ID: P09619

Entrez ID: 5159

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PDGFRB in