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  • The EMBO Journal (2001) 20, 3414 - 3426
  • doi:10.1093/emboj/20.13.3414

PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates

Dominique Davidson1,2 and André Veillette1,2,3,4

  1. Laboratory of Molecular Oncology, IRCM, 110 Pine Avenue West, Montréal, Québec H2W 1R7, Canada
  2. McGill Cancer Centre, 3655 Drummond Street, Montréal, Québec H3G 1Y6, Canada
  3. Department of Medicine, 3655 Drummond Street, Montréal, Québec H3G 1Y6, Canada
  4. Department of Biochemistry, McGill University, 3655 Drummond Street, Montréal, Québec H3G 1Y6, Canada

Correspondence to:

André Veillette, E-mail: veillea@ircm.qc.ca

Received 21 February 2001; Accepted 11 May 2001; Revised 11 May 2001

There is increasing interest in elucidating the mechanisms involved in the negative regulation of lymphocyte activation. Herein, we show that the cytosolic protein tyrosine phosphatase PTP-PEST is expressed abundantly in a wide variety of haemopoietic cell types, including B cells and T cells. In a model B-cell line, PTP-PEST was found to be constitutively associated with several signalling molecules, including Shc, paxillin, Csk and Cas. The interaction between Shc and PTP-PEST was augmented further by antigen receptor stimulation. Overexpression studies, antisense experiments and structure–function analyses provided evidence that PTP-PEST is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of PTP-PEST to induce dephosphorylation of Shc, Pyk2, Fak and Cas, and inactivate the Ras pathway. Taken together, these data suggest that PTP-PEST is a novel and unique component of the inhibitory signalling machinery in lymphocytes.

  • Keywords:

    • inhibition,
    • lymphocyte,
    • phosphatase,
    • PTP-PEST,
    • Shc