platelet-derived growth factor receptor signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by a ligand binding to a platelet-derived growth factor receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:ceb]

The platelet-derived growth factor receptor (PDGFR) signaling pathway is a crucial cellular process that plays a vital role in regulating cell growth, proliferation, differentiation, and survival. This pathway is activated by the binding of platelet-derived growth factor (PDGF) to its cognate receptor, which consists of two transmembrane receptor tyrosine kinases, PDGFR-α and PDGFR-β. Upon ligand binding, these receptors dimerize, bringing their intracellular tyrosine kinase domains into close proximity. This proximity triggers a cascade of phosphorylation events, initiating downstream signaling pathways.

The activation of PDGFRs leads to the phosphorylation of specific tyrosine residues within the receptor itself, creating docking sites for various intracellular signaling molecules. These molecules include the adaptor protein Grb2, which recruits the guanine nucleotide exchange factor SOS. SOS in turn activates the small GTPase Ras, a critical molecular switch in the pathway. Activated Ras then triggers the MAPK/ERK signaling cascade, culminating in the phosphorylation of downstream targets, such as transcription factors, leading to gene expression changes that promote cell proliferation and survival.

In addition to the MAPK/ERK pathway, activated PDGFRs also stimulate other signaling pathways, including the PI3K/Akt pathway. This pathway involves the phosphorylation of phosphatidylinositol 3-kinase (PI3K), which in turn activates the serine/threonine kinase Akt. Akt promotes cell survival by inhibiting apoptosis and enhancing protein synthesis. It also plays a role in cell migration and angiogenesis.

PDGFR signaling is tightly regulated by various mechanisms, including feedback loops and the activity of phosphatases that dephosphorylate activated proteins. These regulatory mechanisms ensure that PDGFR signaling is tightly controlled and does not lead to uncontrolled cell growth or tumor formation.

The PDGFR signaling pathway is implicated in a wide range of biological processes, including development, wound healing, and tissue regeneration. Aberrant PDGFR signaling is associated with various diseases, including cancer, atherosclerosis, and fibrotic diseases. Understanding the intricate details of this pathway is crucial for developing targeted therapies for these diseases.'
"

Proteins (15)

Compounds (1,057)