The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization.
The vav proto-oncogene encodes a protein of unknown function that is rendered oncogenic by loss of a short N-terminal domain. A correction reported here to the vav sequence reveals that a central domain of some 230 amino acids is similar to the products of three genes: the human dbl oncogene, now known to encode a GDP-GTP exchange factor for the Ras-like polypeptide CDC42Hs; the CDC24 gene of Saccharomyces cerevisiae, which participates with CDC42Sc in organization of the cytoskeleton for budding; and the human bcr gene, which recombines with the abl oncogene in certain forms of leukemia. Furthermore, the N-terminal portion of Vav (and of CDC24) is similar to that of certain proteins that associate with filamentous structures. These similarities suggest that Vav, and perhaps also Bcr, may function as a GDP-GTP exchange factor for a Ras-like molecule such as CDC42Hs, and that its action may coordinate cytoplasmic architecture with the cell cycle. Reported evidence that the vav proto-oncogene is widely expressed in hematopoietic cells but not other cell types is extended here by detection of vav mRNA in 49 of 50 murine hematopoietic cell lines representing diverse hematopoietic lineages, and by in situ hybridization in embryos showing expression confined to the only hematopoietic tissue, fetal liver. Thus, like Dbl in other cell types, Vav may function throughout the hematopoietic compartment to govern a Ras-like signal transduction pathway.
Adams
J M
JM
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Houston
H
H
Allen
J
J
Lints
T
T
Harvey
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice / Q000196:embryology; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D051562:Proto-Oncogene Proteins c-bcr; D051567:Proto-Oncogene Proteins c-vav; D012333:RNA, Messenger / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment
C073594:CDC24 protein, S cerevisiae; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; C000715470:MAS1 protein, human; C512843:Mcf2 protein, mouse; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C496619:Vav1 protein, mouse; D011505:Protein-Tyrosine Kinases; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr