Regulation of STAT-dependent pathways by growth factors and cytokines.
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.
Leaman
D W
DW
Department of Molecular Biology, Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
Leung
S
S
Li
X
X
Stark
G R
GR
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic
D016207:Cytokines; D004268:DNA-Binding Proteins; D006133:Growth Substances; D018121:Receptors, Cytokine; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D007372:Interferons; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases