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 from 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 Fcepsilon receptor 1 (FcepsilonRI) modulation in bone marrow-derived mast cells (BMMCs) from me/me and wild-type mice. IL-4 down-regulated FcepsilonRI expression in wild-type BMMCs but had no effect on FcepsilonRI 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.