Vav1: a hematopoietic signal transduction molecule involved in human malignancies.
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.
Katzav
Shulamit
S
The Hubert H. Humphrey Center for Experimental Medicine & Cancer Research, The Hebrew University/Hadassah Medical School, Jerusalem 91120, Israel. shulamitk@ekmd.huji.ac.il
D000818:Animals; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human