VAV BINDING TO HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN (HNRNP)-C - EVIDENCE FOR VAV-HNRNP INTERACTIONS IN AN RNA-DEPENDENT MANNER

The vav proto-oncogene is exclusively expressed in hematopoietic cells and encodes a 95-kDa protein that contains multiple structural domain s, Vav is involved in the expansion of T and B cells, in antigen-media ted proliferative responses, and in the induction of intrathymic T cel l maturation. It becomes rapidly and transiently tyrosine-phosphorylat ed upon triggering of a large number of surface receptors and catalyze s GDP/GTP exchange on Rac-1, We now provide evidence for the specific interaction of Vav with heterogeneous nuclear ribonucleoprotein (hnRNP ) C. Vav and hnRNP C interact both in vivo and in vitro mediated throu gh the carboxyl Src homology 3 domain of Vav and the proline-rich moti f located in the nuclear retention sequence of hnRNP C. More important ly, Vav-hnRNP C complexes are present in living hematopoietic cells an d both proteins localize in the nuclei, mainly on perichromatic fibril s but also on clusters of interchromatin granules. The Vav-hnRNP C int eraction is regulated by poly(U) RNA although a basal association is s till detected in the absence of RNA. Furthermore, RNA homopolymers dif ferentially alter the binding affinity of Vav to hnRNP C and hnRNP K, We propose that Vav-hnRNP interactions may be established in an RNA-de pendent manner.