The vav proto-oncogene product (p95(vav)) is specifically expressed in cells of the hematopoietic system, contains one Src homology 2 and two Src homology 3 domains, and is a substrate for receptor and non-receptor tyrosine kinases. Immunoblotting experiments using an anti-phosphotyrosine monoclonal antibody showed that interferon α (IFNα) induces rapid tyrosine phosphorylation of p95(vav) after binding to its cell surface receptor in the U-266 human myeloma cell line. The IFNα-induced tyrosine phosphorylation of p95(vav) was time- and dose-dependent, confirming the specificity of the process. IFNα-dependent tyrosine phosphorylation of p95(vav) was also observed in other hematopoietic cell lines of B-cell origin (Daudi), T-cell origin (MOLT-4), and promyelocytic origin (HL-60). Immunoprecipitation experiments performed with 32P-labeled U-266 cells and phosphoaminoacid analysis of the bands corresponding to p95(vav) showed that p95(vav) is phosphorylated on serine residues prior to IFNα stimulation of the cells. After IFNα stimulation significant amounts of phosphorylation of p95(vav) on tyrosine residues were detectable. Tyrosine phosphorylation of p95(vav) in U- 266 and HL-60 cells was also induced by two other Type I IFNs, IFNβ and IFNω. Altogether these data suggest that the vav proto-oncogene product is a substrate for a Type I IFN-regulated tyrosine kinase(s) and may be involved in the signal transduction pathway of Type I IFNs in hematopoietic cells.
|Original language||English (US)|
|Number of pages||4|
|Journal||Journal of Biological Chemistry|
|State||Published - Jan 1 1994|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology