SHP-1 regulates STAT6 phosphorylation and IL-4-mediated function in a cell type-specific manner.
SHP-1 has been shown to play positive and negative regulatory roles in IL-4-induced STAT6 phosphorylation and in IL-4-mediated functions. To determine whether SHP-1 can regulate STAT6 phosphorylation and IL-4-mediated functions in a cell type-specific manner in the immune system, we examined the IL-4 receptor (IL-4R) expression, STAT6 phosphorylation, and IL-4-mediated functions in CD4+ and CD8+ T cells of viable motheaten (me(v)/me(v)) and littermate control (+/-) mice. CD4+ T cells as well as CD8+ T cells from the lymph node of me(v)/me(v) and +/- mice expressed comparable levels of IL-4R. In CD4+ T cells, the loss of SHP-1 activity did not affect IL-4-induced STAT6 phosphorylation or IL-4-mediated function. In contrast, SHP-1-deficient CD8+ T cells from me(v)/me(v) mice failed to develop into IL-4-producing type-2 cytotoxic T cells (Tc2) in the presence of IL-4 despite that they showed comparable levels of STAT6 phosphorylation to that of +/- CD8+ T cells. Loss of SHP-1 activity also abolished IL-4-mediated inhibition of c-kit expression in bone marrow-derived mast cell (BMMC). Thus, our data suggest that SHP-1 may regulate IL-4-induced STAT6 phosphorylation and IL-4-mediated functions in a cell type-specific manner.
Huang
Zan
Z
The Department of Cell Biology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Coleman
John M
JM
Su
Yan
Y
Mann
Meredith
M
Ryan
John
J
Shultz
Leonard D
LD
Huang
Hua
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D015847:Interleukin-4 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics; D050800:STAT6 Transcription Factor; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology; D015534:Trans-Activators / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D019009:Proto-Oncogene Proteins c-kit; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse