title: Sulfhydryl-2 domain-containing protein tyrosine phosphatase-1 is not a negative regulator of interleukin-4 signaling in murine mast cells.
abstract: 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.
authors.affiliation: Division of Pulmonary Medicine, Allergy, and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: White
authors.forename: R P
authors.initials: RP
authors.lastname: Andrews
authors.forename: G K
authors.initials: GK
authors.lastname: Hershey
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D017455:Receptors, IgE / Q000378:metabolism; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E; D004247:DNA; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse