Association of the vav proto-oncogene product with poly(rC)-specific RNA-binding proteins.
We have used the yeast two-hybrid system to isolate proteins that interact with the carboxy-terminal SH3-SH2-SH3 region of Vav. One of the clones encoded heterogeneous nuclear ribonucleoprotein K (hnRNP K), a poly(rC)-specific RNA-binding protein. The interaction between Vav and hnRNP K involves the binding of the most carboxy-terminal SH3 domain of Vav to two proline-rich sequences present in the central region of hnRNP K. Overexpression of Vav in mouse fibroblasts leads to the formation of a stable complex with the endogenous hnRNP K and to the preferential redistribution of this protein to the cytoplasmic fraction. More importantly, Vav and hnRNP K proteins also interact in hematopoietic cells. In addition, Vav associates in vitro with a second 45-kDa poly(rC)-specific RNA-binding protein via its SH3-SH2-SH3 region. These results suggest that Vav plays a role in the regulation of the late steps of RNA biogenesis by modulating the function of poly(rC)-specific ribonucleoproteins.
Bustelo
X R
XR
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Suen
K L
KL
Michael
W M
WM
Dreyfuss
G
G
Barbacid
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004591:Electrophoresis, Polyacrylamide Gel; D015723:Gene Library; D006367:HeLa Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011066:Poly C / Q000378:metabolism*; D011392:Proline; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D011519:Proto-Oncogenes; D012332:RNA, Heterogeneous Nuclear / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D013379:Substrate Specificity
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C000715470:MAS1 protein, human; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D012332:RNA, Heterogeneous Nuclear; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; C496618:VAV1 protein, human; D011066:Poly C; D011392:Proline