Protein-tyrosine phosphatase-kappa regulates CD4+ T cell development through ERK1/2-mediated signaling.
T cells express diverse antigen-specific receptors and are required for eradicating pathogens and transformed cells. T cells expressing CD4 acquire helper effector functions and those expressing CD8 exert cytotoxic activity after antigen recognition. The protein-tyrosine phosphatase, receptor type kappa (PTPRKappa) is mutated in LEC rats, resulting in impaired CD4(+) T cell development in the thymus. However, the molecular mechanism of PTPRK controlling CD4(+) T cell development remains unclear. We demonstrate herein that inhibition of PTPRK by transducing a dominant negative form of the intracellular domain of PTPRK (PTPRK-ICD-DN) in bone marrow-derived stem cells suppresses the development of CD4(+) T cells. The inhibition of PTPRK by PTPRK-ICD-DN or short-hairpin RNA for PTPRK attenuates ERK1/2 phosphorylation in T cells after PMA and ionomycin stimulation. Total thymocytes from LEC rats also showed weaker phosphorylation of ERK1/2 after PMA and ionomycin stimulation than control thymocytes. Furthermore, inhibition of PTPRK by PTPRK-ICD-DN suppressed MEK1/2 and c-Raf phosphorylation, which is required for ERK1/2 phosphorylation. These data indicate that PPTRK positively regulates ERK1/2 phosphorylation, which impacts CD4(+) T cell development.
Department of Immunology and Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Namjil
N
Erdenebayar
Yoichi
Y
Maekawa
Jun
J
Nishida
Akiko
A
Kitamura
Koji
K
Yasutomo
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C489852:PTPRK protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2