期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 28, 期 16, 页码 5014-5026出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00640-08
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资金
- NIAID NIH HHS [R01 AI020519, 5R01AI020519-22] Funding Source: Medline
- NIDDK NIH HHS [P30 DK048520] Funding Source: Medline
Although the best-defined function of type H major histocompatibility complex (MHC-II) is presentation of antigenic peptides to T lymphocytes, these molecules can also transduce signals leading alternatively to cell activation or apoptotic death. MHC-II is a heterodimer of two transmembrane proteins, each containing a short cytoplasmic tail that is dispensable for transduction of death signals. This suggests the function of an undefined MHC-II-associated transducer in signaling the death response. Here we describe a novel plasma membrane tetraspanner (MPYS) that is associated with MHC-II and mediates its transduction of death signals. MPYS is unusual among tetraspanners in containing an extended C-terminal cytoplasmic tail (similar to 140 amino acids) with multiple embedded signaling motifs. MPYS is tyrosine phosphorylated upon MHC-II aggregation and associates with inositol lipid and tyrosine phosphatases. Finally, MHC class II-mediated cell death signaling requires MPYS-dependent activation of the extracellular signal-regulated kinase signaling pathway.
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