Protein-tyrosine phosphatase activity of CD45 is activated by sequential phosphorylation by two kinases.
We describe a potential regulatory mechanism for the transmembrane protein-tyrosine phosphatase CD45. Phosphorylation on both tyrosine and serine residues in vitro results in an activation of CD45 specifically toward one artificial substrate but not another. The activation of these kinases appears to be order dependent, as it is enhanced when phosphorylation of tyrosine precedes that of serine but phosphorylation in the reverse order yields no activation. Any of four protein-tyrosine kinases tested, in combination with the protein-serine/threonine kinase, casein kinase II, was capable of mediating this activation in vitro. The time course of phosphorylation of CD45 in response to T-cell activation is consistent with the possibility that this regulatory mechanism is utilized in vivo.
Stover
D R
DR
Department of Biochemistry, University of Washington, Seattle 98195.
Walsh
K A
KA
D000818:Animals; D047390:Casein Kinase II; D002460:Cell Line; D006224:Cricetinae; D004789:Enzyme Activation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000737:chemistry; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D019000:Phosphotyrosine; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology*; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D010748:Phosphopeptides; D010768:Phosphoserine; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases