Subcellular localization of intracellular protein tyrosine phosphatases in T cells

A high protein tyrosine phosphatase (PTPase) activity is required to maintain circulating T lymphocytes in a resting phenotype, and to limit the initiation of T cell activation. We report that 15 of the currently known 24 intracellular PTPases are expressed in T cells, namely HePTP, TCPTP, SHP1, SHP2, PEP, PTP‐PEST, PTP‐MEG2, PTEN, PTPH1, PTP‐MEG1, PTP36, PTP‐BAS, LMPTP, PRL‐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 that essentially excludes them from a direct role in early T cell antigen receptor 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.