Sulfhydryl-2 domain-containing protein tyrosine phosphatase-1 is not a negative regulator of interleukin-4 signaling in murine mast cells

Sulfhydryl-2 domain-containing tyrosine phosphatase-1 (SHP-1) has an important role in the negative regulation of many receptors including the interleukin (IL)-4 receptor. Motheaten mice (me/me) have a homozygous mutation in SHP-1 and do not possess functional SHP-1, Pre-B-cell lines derived front me/me mice have been reported to display prolonged IL-4-dependent activation of signal transducer and activator of transcription-6 (Stat6), We evaluated IL-4-dependent Stat6 activation and Fe epsilon receptor 1 (Fc epsilon RI) modulation in bone marrow-derived mast cells (BMMCs) from me/me and wild-type mice. IL-4 down-regulated Fc epsilon RI expression in wild-type BMMC6 but had no effect on Fc epsilon RI expression in me/me BMMCs, Furthermore, me/me mast cells did not exhibit enhanced or prolonged IL-4-induced Stat6 activation compared with wild-type cells, indicating that mast cells possess alternative tyrosine phosphatases that are responsible for down-regulating Stat6 or can substitute for SHP-1. Thus, SHP-1 is not a negative regulator of IL-4 signaling in BMMCs. These results demonstrate the complexity and cellular specificity of these signaling pathways and indicate a previously unrecognized role for SHP-1 in murine mast cells.