Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway.
Stimulation of T lymphocytes through their antigen receptor (T-cell receptor; TCR) results in the activation of a tyrosine kinase and the generation of phosphatidyl inositol (PtdIns)-derived second messengers. Several reports have indicated that CD45, a haematopoietic cell-specific surface glycoprotein with tyrosine phosphatase activity in its cytoplasmic domain, is important in lymphocyte activation. To examine the possibility that CD45 might influence proximal signal transduction events through the TCR, we have isolated a variant of the human T-cell leukaemic line, HPB-ALL, which fails to express this phosphatase. Unlike cells expressing CD45, stimulation of the TCR in the CD45-negative cell does not result in PtdIns-derived second messengers. Reconstitution of CD45 expression restored early signalling events through the TCR. To localize the site of CD45 action, the human muscarinic type 1 receptor, which also activates the PtdIns second messenger pathway, was transfected into the CD45-negative cell. Although stimulation of the TCR failed to generate PtdIns-derived second messengers, there was normal activity of the PtdIns pathway when human muscarinic receptor type 1 was stimulated, despite the absence of CD45. These data indicate that CD45 influences a cellular component that is essential for effective coupling of the TCR to the PtdIns second messenger pathway.
Koretzky
G A
GA
Department of Medicine, University of California, San Francisco 94143.
Picus
J
J
Thomas
M L
ML
Weiss
A
A
D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000502:physiology*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D017493:Leukocyte Common Antigens; D010716:Phosphatidylinositols / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D006649:Histocompatibility Antigens; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D010749:Phosphoprotein Phosphatases; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium