ASSOCIATION OF THE VAV PROTOONCOGENE PRODUCT WITH POLY(RC)-SPECIFIC RNA-BINDING PROTEINS

We have used the yeast two-hybrid system to isolate proteins that inte ract with the carboxy-terminal SH3-SH2-SH3 region of Vav. One of the c lones encoded heterogeneous nuclear ribonucleoprotein K (hnRNP K), a p oly(rC)-specific RNA-binding protein. The interaction between Vav and hnRNP K involves the binding of the most carboxy-terminal SH3 domain o f Vav to two proline-rich sequences present in the central region of h nRNP K. Overexpression of Vav in mouse fibroblasts leads to the format ion of a stable complex with the endogenous hnRNP K and to the prefere ntial 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 res ults suggest that Vav plays a role in the regulation of the late steps of RNA biogenesis by modulating the function of poly(rC)-specific rib onucleoproteins.