cellular response to platelet-derived growth factor stimulus

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a platelet-derived growth factor stimulus. [GOC:yaf]

Cellular response to platelet-derived growth factor (PDGF) stimulus is a complex process involving multiple signaling pathways that ultimately lead to cell proliferation, differentiation, and survival. Upon binding to its receptor, PDGF triggers a cascade of events:

1. **Receptor Dimerization and Autophosphorylation:** PDGF binds to its receptor, a tyrosine kinase receptor (PDGFR), leading to receptor dimerization. This dimerization activates the receptor's intrinsic tyrosine kinase activity, resulting in autophosphorylation of tyrosine residues within the receptor's cytoplasmic domain.

2. **Recruitment of Signaling Molecules:** Phosphorylated tyrosine residues on the PDGFR serve as docking sites for various signaling molecules, including adaptor proteins, kinases, and phosphatases. These molecules bind to the receptor through specific protein-protein interactions, initiating downstream signaling pathways.

3. **Activation of Ras/MAPK Pathway:** The adaptor protein Grb2 binds to phosphorylated PDGFR and recruits the guanine nucleotide exchange factor (GEF) Sos. Sos activates the small GTPase Ras, which in turn activates a cascade of kinases, including Raf, MEK, and ERK (extracellular signal-regulated kinase). The MAPK pathway promotes cell proliferation and survival.

4. **Activation of PI3K/Akt Pathway:** The PI3 kinase (PI3K) is recruited to the PDGFR and activated. PI3K phosphorylates phosphatidylinositol (PIP2), generating PIP3, which acts as a second messenger. PIP3 activates the protein kinase Akt (also known as PKB). Akt promotes cell survival and inhibits apoptosis.

5. **Activation of PLCγ Pathway:** Phospholipase C gamma (PLCγ) is also recruited to the PDGFR and activated. PLCγ hydrolyzes PIP2, producing diacylglycerol (DAG) and inositol triphosphate (IP3). DAG activates protein kinase C (PKC), which regulates gene expression and cytoskeletal reorganization. IP3 mobilizes calcium from intracellular stores, leading to various cellular responses, including cytoskeletal rearrangements and gene expression changes.

6. **Transcriptional Regulation:** Activated signaling pathways, such as the MAPK and PI3K/Akt pathways, ultimately regulate gene expression. They activate transcription factors, such as c-Fos and c-Jun, which bind to DNA and regulate the expression of genes involved in cell proliferation, differentiation, and survival.

7. **Cellular Responses:** The integrated responses of various signaling pathways lead to diverse cellular responses, including:
* **Cell Proliferation:** PDGF promotes cell division and growth by stimulating the expression of genes involved in cell cycle progression and DNA synthesis.
* **Cell Differentiation:** PDGF can influence the differentiation of specific cell types, depending on the cellular context and the presence of other growth factors.
* **Cell Survival:** PDGF promotes cell survival by inhibiting apoptotic pathways and promoting the expression of anti-apoptotic genes.
* **Migration and Motility:** PDGF promotes cell migration and motility by regulating cytoskeletal rearrangements and cell adhesion.

In summary, cellular response to PDGF involves a complex interplay of multiple signaling pathways that ultimately lead to diverse cellular responses, including cell proliferation, differentiation, survival, migration, and motility.'
"

Proteins (9)

Compounds (1,156)