An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth

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作者：

AD Keegan，K Nelms，M White，LM Wang，JH Pierce，WE Paul

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摘要：

Interleukin-4 (IL-4) treatment of 32D cells overexpressing insulin receptor substrate 1 (IRS-1) causes prompt tyrosine phosphorylation of IRS-1. Transfection of truncation mutants of the human IL-4 (huIL-4) receptor into 32D-IRS-1 cells demonstrated that the region from amino acid 437–557 is important for IL-4 signaling. This region of the IL-4 receptor (IL-4R) contains the motif 488 PL-X4-NPXYXSXSD 502 (insulin/IL-4R [I4R]) found in the insulin and insulin-like growth factor 1 receptors. Mutation of Y497 to F yielded receptors that caused little or no IRS-1 phosphorylation in response to huIL-4 when expressed in 32D-IRS-1 cells. Most cell lines expressing Y497F also failed to proliferate in response to huIL-4. Furthermore, a glutathione-S-transferase fusion protein containing the I4R motif-bound IRS-1, tyrosine kinase(s), and other unidentified phosphoproteins with molecular sizes of 140, 80, and 55 kd. Thus, the central tyrosine of the I4R motif has a major role in IL-4-mediated signal transduction in 32D cells.

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关键词：

Animals Rats Phosphoproteins Receptors, Interleukin-4 Receptors, Mitogen Sequence Alignment Signal Transduction Consensus Sequence Sequence Homology, Amino Acid Phosphorylation