Regulation of the p59fyn protein tyrosine kinase by the CD45 phosphotyrosine phosphatase.
Triggering of the T cell antigen receptor/CD3 (TcR/CD3) complex leads to rapid tyrosine phosphorylation of regulatory proteins that participate in initiating T cell activation and proliferation. This signal transduction event requires the presence of the TcR/CD3-associated protein tyrosine kinase p59fyn. There is also evidence that the CD45 phosphotyrosine phosphatase is involved in TcR/CD3 signalling. We show here by capping experiments using double indirect immunofluorescence techniques that the receptor phosphotyrosine phosphatase CD45 and the intracellular protein tyrosine kinase p59fyn specifically co-distribute in functional T lymphocytes. Furthermore, we provide evidence that isolated p59fyn is a substrate for CD45 as indicated by the rapid dephosphorylation of the regulatory Tyr531 of p59fyn by CD45. This dephosphorylation is accompanied by a severalfold increase in the catalytic activity of p59fyn as measured by its autophosphorylation and phosphorylation of an exogenous substrate. We also demonstrate that CD45-mediated dephosphorylation and activation of p59fyn apparently occurs at a slow basal rate in resting T cells. This represents the first identification of a physiologic regulator of p59fyn and implies a mechanism for the role of CD45 in TcR/CD3 signal transduction.
Mustelin
T
T
Department of Pathology, University of Helsinki, Finland.
Pessa-Morikawa
T
T
Autero
M
M
Gassmann
M
M
Andersson
L C
LC
Gahmberg
C G
CG
Burn
P
P
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D006649:Histocompatibility Antigens / Q000032:analysis / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000276:immunology; D051076:Proto-Oncogene Proteins c-fyn; D011817:Rabbits
D015703:Antigens, CD; D006649:Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases