TYROSINE PHOSPHORYLATION OF VCP, THE MAMMALIAN HOMOLOG OF THE SACCHAROMYCES-CEREVISIAE CDC48 PROTEIN, IS UNUSUALLY SENSITIVE TO STIMULATIONBY SODIUM VANADATE AND HYDROGEN-PEROXIDE

A mAb produced by immunization of mice with tyrosine-phosphorylated pr oteins from activated B lymphocytes was found to recognize valosin-con taining protein (VCP). VCP is the mammalian homologue of the Saccharom yces cerevisiae CDC48 protein and has localized regions of sequence id entity with the yeast Sec18 and Pas1 proteins and the mammalian NSF pr otein, all of which are important in intracellular vesicular traffic o r formation. VCP was found to be constitutively phosphorylated on tyro sine in Rous sarcoma virus-transformed fibroblasts. Phosphorylation of VCP on tyrosine was stimulated only modestly during activation of B l ymphocytes by ligation of membrane Ig. In contrast, treatment of B cel ls with either H2O2 or a combination of H2O2 and Na3VO4 greatly increa sed tyrosine phosphorylation of VCP. These results may suggest that un der normal conditions tyrosine phosphorylation of VCP has a rapid turn over and that it can be detected easily only when dephosphorylation is inhibited by artificial means.