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 domains. Vav is involved in the expansion of T and B cells, in antigen-mediated proliferative responses, and in the induction of intrathymic T cell maturation. It becomes rapidly and transiently tyrosine-phosphorylated upon triggering of a large number of surface receptors and catalyzes 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 through the carboxyl Src homology 3 domain of Vav and the proline-rich motif located in the nuclear retention sequence of hnRNP C. More importantly, Vav-hnRNP C complexes are present in living hematopoietic cells and both proteins localize in the nuclei, mainly on perichromatic fibrils but also on clusters of interchromatin granules. The Vav-hnRNP C interaction is regulated by poly(U) RNA, although a basal association is still detected in the absence of RNA. Furthermore, RNA homopolymers differentially alter the binding affinity of Vav to hnRNP C and hnRNP K. We propose that Vav-hnRNP interactions may be established in an RNA-dependent manner.
Romero
F
F
Institut Cochin de Genetique Moleculaire, U363 INSERM, Hopital Cochin, 27 rue du Faubourg Saint Jacques, 75014 Paris, France. romero@icgm.cochin.inserm.fr
Germani
A
A
Puvion
E
E
Camonis
J
J
Varin-Blank
N
N
Gisselbrecht
S
S
Fischer
S
S
D002460:Cell Line; D003001:Cloning, Molecular; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D016253:Microscopy, Immunoelectron; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; D012313:RNA / Q000378:metabolism / Q000494:pharmacology; D012260:Ribonucleases / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D018909:src Homology Domains / Q000502:physiology
D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; D012261:Ribonucleoproteins; C496618:VAV1 protein, human; D012313:RNA; D012260:Ribonucleases