Regulation of the p70zap tyrosine protein kinase in T cells by the CD45 phosphotyrosine phosphatase.
Two classes of protein tyrosine kinases (PTK) are utilized by the T cell antigen receptor (TcR)/CD3 complex for initiation of the signaling cascade, the Src-family PTK p56lck and p59fyn, and the Syk-family PTK p70zap and p72syk. In addition, the CD45 phosphotyrosine phosphatase (PTPase) is required for the induction of tyrosine phosphorylation by the TcR/CD3, presumably by positively regulating Src-family PTK. Here we report that CD45 also regulates the Syk-family PTK p70zap (or ZAP-70). In CD45-negative T cells, p70zap was constitutively phosphorylated on tyrosine and co-immunoprecipitated with the TcR-zeta chain. In resting wild-type CD45-positive cells, p70zap was mainly unphosphorylated, but it was rapidly phosphorylated on tyrosine upon treatment of the cells with anti-CD3 or PTPase inhibitors. Finally, p70zap co-distributed with CD45 in intact T cells, and tyrosine phosphorylated p70zap was dephosphorylated by CD45 in vitro. These findings suggest that CD45 plays an important role, direct or indirect, in the regulation of p70zap and its function in TcR/CD3 signaling.
Mustelin
T
T
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, CA 92037, USA.
Williams
S
S
Tailor
P
P
Couture
C
C
Zenner
G
G
Burn
P
P
Ashwell
J D
JD
Altman
A
A
D002461:Cell Line, Transformed; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases