Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway

Gary A. Koretzky, Joel Picus, Matthew L. Thomas, Arthur Weiss

Research output: Contribution to journalArticlepeer-review

391 Scopus citations

Abstract

STIMULATION of T lymphocytes through their antigen receptor (T-cell receptor; TCR) results in the activation of a tyrosine kinase1,2 and the generation of phosphatidyl inositol (PtdIns)-derived second messengers3-5. Several reports have indicated that CD45, a haematopoetic cell-specific surface glycoprotein with tyrosine phosphatase activity in its cytoplasmic domain6-10, is important in lymphocyte activation11-14. 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 Ptdlns second messenger pathway15,16, was transfected into the CD45-negative cell. Although stimulation of the TCR failed to generate Ptdlns-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.

Original languageEnglish
Pages (from-to)66-68
Number of pages3
JournalNature
Volume346
Issue number6279
DOIs
StatePublished - 1990

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