p38 MAPK activation by VEGFR

Stable Identifier
R-HSA-5218804
Type
Reaction [omitted]
Species
Homo sapiens
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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).

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Catalyst Activity
Title
MAP kinase kinase activity of VEGFA:p-6Y-VEGFR2:NCK:p-S21,Y420-FYN:p-3Y-PAK2:CDC42:GTP [plasma membrane]
Physical Entity
Activity
Orthologous Events
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