p95(vav) associates with the type I interferon (IFN) receptor and contributes to the antiproliferative effect of IFN-alpha in megakaryocytic cell lines.
The vav proto-oncogene product is a 95 kDa protein predominantly expressed in hematopoietic cells. Vav presents a wide range of functional domains, including structural domains known to be involved in signal transduction. Triggering of various cytokine receptors among which type I interferon receptor induces a rapid and transient tyrosine phosphorylation of p95(vav). Nevertheless, the biological functions of p95(vav) are still unclear. This report is the first documentation on the physical association of p95(vav) with both alpha and beta type I interferon receptor chains, as demonstrated by co-immunoprecipitation and Western blot analysis in megakaryocytic cells (Dami and UT7). This interaction is increased by interferon-alpha/beta stimulation. Moreover, p95(vav) phosphorylated subsequently to type I interferon treatment, is translocated in the nucleus; a concomitant increase of its association with the regulatory subunit of the nuclear DNA-dependent protein kinase, KU-70 is observed in the nucleus. To determine whether p95(vav) participates in the biological response to type I interferons, we studied the effects of non modified Vav oligodeoxynucleotides on the antiproliferative effect of interferon-alpha on megakaryocytic cells. By this oligodeoxynucleotide strategy, we show that p95(vav) contributes greatly to the cell proliferation inhibition induced by type I IFN.
Micouin
A
A
Unité 365 INSERM, Institut Curie, Section Recherche, Paris, France.
Wietzerbin
J
J
Steunou
V
V
Martyré
M C
MC
D001692:Biological Transport; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016259:Genes, myc; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008533:Megakaryocytes / Q000187:drug effects* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D017471:Receptors, Interferon / Q000502:physiology*
D018797:Cell Cycle Proteins; D007370:Interferon Type I; C000715470:MAS1 protein, human; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D017471:Receptors, Interferon; C496618:VAV1 protein, human