Regulation of Vav proteins by intramolecular events.
The Vav family is a group of signal transduction molecules with oncogenic potential that play important roles in development and cell signaling. The function of Vav proteins co-evolved with tyrosine kinase pathways, probably to assure the optimal conversion of extracellular signals into intracellular responses coupled to the cytoskeleton and the transcriptome. To date, the best-known function of Vav proteins is their role as GDP/GTP exchange factors for Rho/Rac molecules. This activity is highly regulated during signal transduction by processes involving intramolecular interactions among several domains of Vav proteins. On one hand, the phosphorylation of Vav proteins on a specific tyrosine residue leads to a conformational change that allows the activation of the catalytic activity of Vav proteins. This mechanism of activation has been recently explained in structural terms and shown to involve the acidic and Dbl-homology domains of Vav. On the other hand, the activity of Vav proteins is affected by a second type of intramolecular interaction occurring between the plekstrin-homology and the catalytic regions of Vav that is regulated by phospholipids. In this review, we will give a brief overview of the recent advances in this field.
Bustelo
Xosé R
XR
Centro de Investigacion del Cáncer and Instituto de Biologia Molecular y Celular del Cáncer. University of Salamanca-CSIC. 37007 Salamanca, Spain. xbustelo@usal.es
D000818:Animals; D018797:Cell Cycle Proteins; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000502:physiology; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav
D018797:Cell Cycle Proteins; D008055:Lipids; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human