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Human hematopoietic cells express two forms of thecytokine receptor common γ-chain (γc)

Cell Research 1997年第2期7卷 195-205页

作者： SHI YU FANG MARY HILL ANTON NOVAK ZHIQING CHEN RUO XIANG WANG CHOONGCHIN LIEW GORDON B. MILLS (Oncology Research, The Toronto Hospital, 200 ElizabcthSt., Toronto, Ontario, Canada MSG 2C4Department of Immunology, Holland Laboratoryof American Red Cr Oncology Research The Toronto Hospital Toronto Canada Department of Immunology Holland Laboratory of American Red Cross Rockville USA Department of Genetics Research Institute The Hospital for Sick Children Toronto Canada Department of Clinical Biochemistry University of Toronto Toronto Canada Department of Molecular Oncology MD Anderson Cancer Center University of Texas Houston

Recent studies have revealed that the γ-chain of theIL-2 receptor is shared by the receptors for IL-4, IL7, IL-9, IL-13, and IL-15, and it is therefore also referred toas the common γ-chain (γc). Mutations of γc result inX-linked severe combined immunodeficiency syndrome inhumans, indicating that rye is essential for normal development and function of the immune system. We demonstratethat human hematopoietic cells express two γc transcriptsdiffering in their carboxyl terminal coding region. Onetranscript is the previously reported sequence (γc-long),whereas the newly identified sequence exhibits a deletion of72 nucleotides close to the 3'-end of the open reading frame(γc-short). This alteration predicts a loss of 24 amino acidsincluding a conserved tyrosine residue which is shared byseveral members of the cytokine receptor family. Thepresence of these two distinct forms of rye transcripts wasdemonstrated by sequencing of reversely transcribed andpolymerase chain reaction (RT-PCR) amplified mRNA, restriction digestion of the RT-PCR products, RNAse protection, and Northern blotting from human cell lines andhuman peripheral blood lymphocytes. Furthermore, thetwo variants were present in peripheral blood lymphocytesfrom both female and male donors, which rules out allelicvariants since rye is a single copy gene located on the Xchromosome. A truncation mutant at a site near the observed changes in γc-short has been reported by othersto alter biochemical events activated by cytokines. Thiscombined with the loss of a potential SH2 "docking" sitein γc-short suggests that γc-long and γc-short may link todifferent signaling pathways and may play an importantrole in determining the cellular response to IL-2, IL-4, IL-7, IL-9, IL-13, IL-15.

关键词： IL-2 receptor γ-chain cytokine receptor common γ-chain IL-2 receptor cytokine receptors RNA splicing

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