Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PDGFRB (P09619) - Overview - Molecular Target Synopsis

Protein


PDGFRB, Platelet-derived growth factor receptor beta
Enzyme Classification 2.7.10.1
UniProt P09619

Also Known as PGFRB_HUMAN, PDGFRB, PDGFR, PDGFR1

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. Interacts with homodimeric PDGFB and PDGFD, and with heterodimers formed by PDGFA and PDGFB. May also interact with homodimeric PDGFC. Monomer in the absence of bound ligand. Interaction with homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD, leads to receptor dimerization, where both PDGFRA homodimers and heterodimers with PDGFRB are observed. Interacts with SH2B2/APS. Interacts directly (tyrosine phosphorylated) with SHB. Interacts (tyrosine phosphorylated) with PIK3R1 and RASA1. Interacts (tyrosine phosphorylated) with CBL. Interacts (tyrosine phosphorylated) with SRC and SRC family kinases. Interacts (tyrosine phosphorylated) with PIK3C2B, maybe indirectly. Interacts (tyrosine phosphorylated) with SHC1, GRB7, GRB10 and NCK1. Interaction with GRB2 is mediated by SHC1. Interacts (via C-terminus) with SLC9A3R1.

2L6W
PDGFR BETA-TM
RCSB/PDB
Inspect Structure
See all 3D Structures for PDGFRB

Isoforms / Transcripts (Protein Coding)


Drugs


PDGFRB is targeted by Approved Drugs Imatinib, Axitinib, Sunitinib, Sorafenib, Dasatinib, Pazopanib, Becaplermin. (see details)
Imatinib
Axitinib
Sunitinib
Sorafenib
Dasatinib
Pazopanib
Becaplermin

Sub-cellular localization


UniProt: PDGFRB is active in the following subcellular-locations: cell membrane, cytoplasmic vesicle, lysosome lumen.
GO terms: PDGFRB is active in the following subcellular-locations: apical plasma membrane, cell surface, cytoplasm, cytoplasmic vesicle, focal adhesion, Golgi apparatus, integral component of plasma membrane, intracellular membrane-bounded organelle, intrinsic component of plasma membrane, lysosomal lumen, membrane, nucleus, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PDGFRB has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SF_539, HS578T, HOP_62

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 255.T, Hs 940.T, G142

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, BJ, IMR-90

(see details)

RNA Interference


PDGFRB was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: H460, A549. (see details)

3D Structures


For PDGFRB there are:
7 structures (10 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PDGFRB has been screened with 3203 compounds (4660 bioactivities), 804 compounds have bioactivities that show binding affinity of <= 500nM (1108 bioactivities). (see details)