Biochemical characterization of valosin-containing protein, a protein tyrosine kinase substrate in hematopoietic cells

• Published in: The Journal of biological chemistry 1994-04, Vol.269 (15), p.11435-11441
• Main Authors: EGERTON, M, SAMELSON, L. E
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - metabolism; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - isolation & purification; Cell Cycle Proteins - metabolism; Cell Line; Clathrin - isolation & purification; Clathrin - metabolism; Cytoskeletal Proteins; Enzymes and enzyme inhibitors; Female; Fundamental and applied biological sciences. Psychology; Hydrolases; Intercellular Signaling Peptides and Proteins; Isoenzymes - chemistry; Isoenzymes - metabolism; Lymphocytes - metabolism; Macromolecular Substances; Mice; Mice, Mutant Strains; Molecular Sequence Data; Oncogene Proteins - chemistry; Oncogene Proteins - metabolism; Peptides - analysis; Phosphopeptides - chemistry; Phosphopeptides - isolation & purification; Phosphoproteins - chemistry; Phosphoproteins - metabolism; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-vav; Receptors, Antigen, T-Cell - chemistry; Receptors, Antigen, T-Cell - metabolism; Sequence Homology, Amino Acid; Substrate Specificity; Type C Phospholipases - chemistry; Type C Phospholipases - metabolism; Valosin Containing Protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)78142-3

Engagement of the T cell antigen receptor (TCR) leads to activation of multiple tyrosine kinases and rapid tyrosine phosphorylation of intracellular protein substrates. A number of these substrates have been identified and they include TCR subunits, phospholipase C-gamma 1, p95vav, and ezrin. In a recent study we have demonstrated that VCP (valosin-containing protein) becomes tyrosine phosphorylated upon TCR cross-linking. Analysis of the predicted amino acid sequence of this protein indicates that it is a member of a family of oligomeric proteins containing duplicated domains with predicted ATPase activity. In the current study we determine the site of tyrosine phosphorylation in VCP, demonstrate that murine VCP indeed is an oligomeric ATPase, and show that the tyrosine phosphorylation of the protein has no effect on VCP ATPase activity. Recent evidence suggests that VCP associates with clathrin. A possible role of tyrosine phosphorylation in regulating this protein-protein interaction is discussed.