Subcellular localization of intracellular protein tyrosine phosphatases inT cells

A high protein tyrosine phosphatase (PTPase) activity is required to mainta in circulating T lymphocytes in a resting phenotype, and to limit the initi ation of T cell activation. We report that 15 of the currently known 24 int racellular PTPases are expressed in T cells, namely HePTP, TCPTP, SHP1, SHP 2, PEP, PTP-PEST, PTP-MEG2, PTEN, PTPH1, PTP-MEG1, PTP36, PTP-BAS, LMPTP, P RL-1 and OV-1. Most were found in the cytosol and many were enriched at the plasma membrane. Only TCPTP and PTP-MEG2 had subcellular localizations tha t essentially excludes them from a direct role in early T cell antigen rece ptor signaling events. Overexpression of 6 of the PTPases reduced IL-2 gene activation, 3 of them thereby identified as novel candidates for negative regulators of TCR signaling. Our findings expand the repertoire of PTPases that should be considered for a regulatory role in T cell activation.