Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 41, Issue 6, Pages 1245-1248Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2008.11.006
Keywords
Vav1; GEF; Rac; Immunological synapse; NFAT
Categories
Funding
- Israel Academy of Sciences
- Israel Cancer Research Foundation
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Vav1 encodes a unique protein with several motifs known to play a role in tyrosine mediated signal transduction, including a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a Src homology 2 (SH2) domain, and two Src homology 3 (SH3) domains. Physiological Vav1 expression is restricted to the hematopoietic system, where it functions primarily as a specific GDP/GTP nucleotide exchange factor (GEF), a function strictly regulated by tyrosine phosphorylation. In hematopoietic cells, Vav1 is phosphorylated following cell surface receptor activation, triggering re-organization of the cytoskeleton and regulation of other cellular functions including transcription, cytokine production, cell cycle progression, and Ca(2+) mobilization. Vav1 also functions as an adapter, facilitating interaction between other proteins. A truncated Vav1 was first isolated as an oncogene, and its wild-type form has recently been implicated in mammalian malignancies. These properties make Vav1 a promising target for new therapeutic approaches to organ transplantation and cancer therapy. (C) 2008 Elsevier Ltd. All rights reserved.
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