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Positive and negative regulation of antigen receptor signaling by the Shc family of protein adapters
Author(s) -
Finetti Francesca,
Savino Maria Teresa,
Baldari Cosima T.
Publication year - 2009
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2009.00826.x
Subject(s) - biology , caenorhabditis elegans , signal transducing adaptor protein , microbiology and biotechnology , signal transduction , receptor , gene isoform , drosophila melanogaster , immune system , antigen , model organism , phenotype , genetics , gene
Summary: The Shc adapter family includes four members that are expressed as multiple isoforms and participate in signaling by a variety of cell‐surface receptors. The biological relevance of Shc proteins as well as their variegated function, which relies on their highly conserved modular structure, is underscored by the distinct and dramatic phenotypic alterations resulting from deletion of individual Shc isoforms both in the mouse and in two model organisms, Drosophila melanogaster and Caenorhabditis elegans . The p52 isoform of ShcA couples antigen and cytokine receptors to Ras activation in both lymphoid and myeloid cells. However, the recognition of the spectrum of activities of p52ShcA in the immune system has been steadily expanding in recent years to other fundamental processes both at the cell and organism levels. Two other Shc family members, p66ShcA and p52ShcC/Rai, have been identified recently in T and B lymphocytes, where they antagonize survival and attenuate antigen receptor signaling. These developments reveal an unexpected and complex interplay of multiple Shc proteins in lymphocytes.