vascular endothelial growth factor signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by vascular endothelial growth factor (VEGF) binding its receptor on the surface of the target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:signaling, PMID:17470632]

Vascular endothelial growth factor (VEGF) signaling pathway is a critical regulator of angiogenesis, the formation of new blood vessels. It plays a crucial role in various physiological processes, including embryonic development, wound healing, and tissue repair. The pathway is initiated by the binding of VEGF to its receptors, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1), which are tyrosine kinase receptors expressed on the surface of endothelial cells. Binding of VEGF to VEGFR2 triggers a cascade of downstream signaling events, leading to the activation of various intracellular pathways, including the MAPK, PI3K/Akt, and PLCγ pathways.

The MAPK pathway promotes cell proliferation and survival, while the PI3K/Akt pathway regulates cell survival, migration, and permeability. The PLCγ pathway is involved in the regulation of endothelial cell migration and tube formation. VEGF signaling also activates transcription factors such as HIF-1α, which promotes the expression of genes involved in angiogenesis.

Here is a detailed description of the major steps involved in the VEGF signaling pathway:

1. **VEGF Binding and Receptor Dimerization:** VEGF binds to its receptors, VEGFR1 and VEGFR2, leading to the dimerization of the receptors.
2. **Tyrosine Kinase Activation:** Upon dimerization, the intrinsic tyrosine kinase activity of VEGFR2 is activated, leading to phosphorylation of tyrosine residues within the receptor's cytoplasmic domain.
3. **Recruitment of Signaling Molecules:** Phosphorylated tyrosine residues on VEGFR2 serve as docking sites for adaptor proteins and signaling molecules, including PI3K, PLCγ, and Shc.
4. **Activation of Downstream Pathways:**
* **PI3K/Akt pathway:** PI3K is recruited to the receptor and phosphorylates PIP2 to generate PIP3, which activates Akt. Akt promotes cell survival, migration, and angiogenesis.
* **MAPK pathway:** Shc binds to the receptor and activates the Ras-Raf-MEK-ERK cascade, leading to cell proliferation and survival.
* **PLCγ pathway:** PLCγ is activated by the receptor and hydrolyzes PIP2 to generate IP3 and DAG. IP3 releases calcium from intracellular stores, while DAG activates PKC, leading to the regulation of endothelial cell migration and tube formation.
5. **Transcriptional Regulation:** VEGF signaling also activates transcription factors such as HIF-1α, which promotes the expression of genes involved in angiogenesis.

The VEGF signaling pathway is tightly regulated to ensure proper angiogenesis. Dysregulation of this pathway can contribute to various diseases, including cancer, diabetic retinopathy, and rheumatoid arthritis.

This detailed description highlights the complex and intricate nature of the VEGF signaling pathway, emphasizing its critical role in regulating angiogenesis and various physiological processes. The pathway involves multiple signaling molecules, downstream pathways, and transcription factors, all working together to mediate the formation of new blood vessels.'
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Proteins (11)

Compounds (516)