Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo.
Mast cells play a critical role in allergic reactions. The cross-linking of FcεRI-bound IgE with multivalent antigen initiates a cascade of signaling events leading to mast cell activation. It has been well-recognized that cross linking of FcεRI mediates tyrosine phosphorylation. However, the mechanism involved in tyrosine dephosphorylation in mast cells is less clear. Here we demonstrated that protein tyrosine phosphatase 1B (PTP1B)-deficient mast cells showed increased IgE-mediated phosphorylation of the signal transducer and activator of transcription 5 (STAT5) and enhanced production of CCL9 (MIP-1γ) and IL-6 in IgE-mediated mast cells activation in vitro. However, IgE-mediated calcium mobilization, β-hexaosaminidase release (degranulation), and phosphorylation of IκB and MAP kinases were not affected by PTP1B deficiency. Furthermore, PTP1B deficient mice showed normal IgE-dependent passive cutaneous anaphylaxis and late phase cutaneous reactions in vivo. Thus, PTP1B specifically regulates IgE-mediated STAT5 pathway, but is redundant in influencing mast cell function in vivo.
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, Yunnan 650118, China.
Ting
T
Yang
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, Yunnan 650118, China.
Zhongping
Z
Xie
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, Yunnan 650118, China.
Hua
H
Li
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, Yunnan 650118, China.
Lei
L
Yue
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada.
Zheng
Z
Pang
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada.
Adam J
AJ
MacNeil
Goodman Cancer Research Centre and the Department of Biochemistry, McGill University, 1160 Pine Ave. West, Montréal, QC H3A 1A3, Canada.
Michel L
ML
Tremblay
Institute of Medical Physics and Engineering, Tsinghua University, Beijing 100084, China.
Jin-Tian
JT
Tang
The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, Yunnan 650118, China; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada; Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada; Beatrice Hunter Cancer Research Institute, Halifax, Nova Scotia B3K 6R8, Canada. Electronic address: tong-jun.lin@dal.ca.
Tong-Jun
TJ
Lin
D000818:Animals; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D010766:Phosphorylation / Q000235:genetics; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism
C095218:Ccl9 protein, mouse; D019742:Chemokines, CC; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D050799:STAT5 Transcription Factor; D015847:Interleukin-4; D007073:Immunoglobulin E; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse
Allergy; IgE; Mast cells; Protein tyrosine phosphatase