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Reciprocal Signaling Roles for STAT3 and SHP2

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Science  11 Feb 2000:
Vol. 287, Issue 5455, pp. 933
DOI: 10.1126/science.287.5455.933h

One subunit of the receptor for the cytokine interleukin-6 (IL-6) is gp130. Tyrosine phosphorylation of gp130 recruits both protein phosphatase 2 (SHP2) and signal transducer and activator 3 (STAT3). Ohtani et al. utilized knock-in technology to create mice deficient in only the gp130-mediated SHP2 pathway or the gp130-mediated STAT3 pathway to identify the functions of these two pathways. STAT3 signaling was required for embryonic development, whereas SHP2 signaling-deficient mice were viable and fertile. Reciprocal roles for signaling via STAT3 (positive) and SHP2 (negative) were found for cytokine production in T cells and immunoglobulin responses in B cells, consistent with the observation that eliminating the SHP2 pathway resulted in prolonged IL-6-induced STAT3 phosphorylation.—NG

Immunity12, 95 (2000).

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