Regulation of signal transducer and activator of transcription signaling by the tyrosine phosphatase PTP-BL.
Signal Transducer and Activator of Transcription (STAT) proteins are a family of latent cytoplasmic transcription factors that are activated by tyrosine phosphorylation after cytokine stimulation. One mechanism by which STAT signaling is regulated is by dephosphorylation through the action of protein tyrosine phosphatases (PTP). We have identified PTP-Basophil like (PTP-BL) as a STAT PTP. PTP-BL dephosphorylates STAT proteins in vitro and in vivo, resulting in attenuation of STAT-mediated gene activation. In CD4(+) T cells, PTP-BL deficiency leads to increased and prolonged activation of STAT4 and STAT6, and consequently enhanced T helper 1 (Th1) and Th2 cell differentiation. Taken together, our findings demonstrate that PTP-BL is a physiologically important negative regulator of the STAT signaling pathway.
Nakahira
Masakiyo
M
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Tanaka
Takashi
T
Robson
Bryanne E
BE
Mizgerd
Joseph P
JP
Grusby
Michael J
MJ
D000818:Animals; D001491:Basophils / Q000201:enzymology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008817:Mice, Mutant Strains; D017027:Protein Tyrosine Phosphatases / Q000276:immunology* / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D050791:STAT Transcription Factors; D017027:Protein Tyrosine Phosphatases