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The FASEB Journal, Vol 10, 1578-1588, Copyright © 1996 by The Federation of American Societies for Experimental Biology

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Regulation of STAT-dependent pathways by growth factors and cytokines

DW Leaman, S Leung, X Li and GR Stark
Department of Molecular Biology, Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.

Polypeptide growth factors and cytokines elicit their effects by activating specific cell-surface receptors, thereby initiating signaling cascades that culminate in the induction of specific subsets of genes. Initially identified as the primary mediators of interferon- dependent signaling, JAKs and STATs are now known to be utilized by many different extracellular signaling proteins. In this report we describe how JAK-STAT pathways transduce signals initiated by both cytokines and growth factors, focusing on how specificity is achieved through STAT-receptor interactions and on how receptor-associated kinases function in STAT activation. We also summarize current information on interactions between signaling pathways, particularly STAT-Ras cross-talk and the relative importance of these two pathways in regulating the transcription of target genes.


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