Reactome | p38 MAPK activation by VEGFR

p38 MAPK activation by VEGFR

Stable Identifier

R-HSA-5218804

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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In primary cultured human umbilical vein endothelial cells (HUVECs) VEGF-induced activation of SAPK2/p38MAPK, and pharmacological inhibition of p38MAPK attenuated VEGF-induced cell migration (Rouseseau et al. 1997, 2000). The p38MAPK pathway conveys the VEGF signal to microfilaments inducing rearrangements of the actin cytoskeleton. These actin structures are thought to generate the contractile force within cells that is required for endothelial cell migration. Activation of p38 requires the activity of FYN and PAK2 (Lamalice et al. 2004). However, little is known of the exact molecular events that follow activation of PAK2 and lead to p38 activation. Like all MAP kinases, p38 MAP kinases are activated by dual kinases termed the MAP kinase kinases (MKKs). There are two main MAPKKs that are known to activate p38, MKK3 and MKK6 (Zarubin & Han 2005). Along with FYN and PAK these MKKs might contribute to the activation of p38. Activation of p38 resulted in activation of MAP kinase activated protein kinase 2/3 (MAPK 2/3) and phosphorylation of the F-actin polymerization modulator, heat shock protein 27 (HSP27) (Rousseau et al. 1997).

Literature References

PubMed ID	Title	Journal	Year
9393975	p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells Rousseau, S, Houle, F, Landry, J, Huot, J	Oncogene	1997
10744763	Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requires concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosphorylation of focal adhesion kinase Waltenberger, J, Kotanides, H, Rousseau, S, Houle, F, Landry, J, Huot, J, Witte, L	J. Biol. Chem.	2000