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.
Laboratory of Signal Transduction, La Jolla Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
A
A
Gjörloff-Wingren
M
M
Saxena
S
S
Han
X
X
Wang
A
A
Alonso
M
M
Renedo
P
P
Oh
S
S
Williams
J
J
Schnitzer
T
T
Mustelin
D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D003599:Cytoskeleton / Q000201:enzymology; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006413:Hematopoietic System / Q000201:enzymology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000201:enzymology; D017027:Protein Tyrosine Phosphatases / Q000032:analysis*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000648:ultrastructure
D017027:Protein Tyrosine Phosphatases