Abstract
Genetic and biochemical studies have led to the identification of the Stat3-Interacting Protein StIP1. The preferential association of StIP1 with inactive (i.e., unphosphorylated) Stat3 suggests that it may contribute to the regulation of Stat3 activation. Consistent with this possibility, StIP1 also exhibits an affinity for members of the Janus kinase family. Overexpression of the Stat3-binding domain of StIP1 blocks Stat3 activation, nuclear translocation, and Stat3-dependent induction of a reporter gene. These studies indicate that StIP1 regulates the ligand-dependent activation of Stat3, potentially by serving as a scaffold protein that promotes the interaction between Janus kinases and their Stat3 substrate. The ability of StIP1 to associate with several additional members of the signal transducer and activator of transcription family suggests that StIP1 may serve a broader role in cytokine-signaling events.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Cell Line
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Cytokines / physiology*
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DNA-Binding Proteins / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins*
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Mice
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Molecular Sequence Data
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Protein Biosynthesis
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Protein-Tyrosine Kinases / metabolism
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Recombinant Proteins / metabolism
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STAT3 Transcription Factor
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Sequence Alignment
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Sequence Homology, Amino Acid
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Signal Transduction / physiology*
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Trans-Activators / metabolism*
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Transcription, Genetic*
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Transfection
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Tumor Cells, Cultured
Substances
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Carrier Proteins
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Cytokines
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DNA-Binding Proteins
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ELP2 protein, human
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Elp2 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Recombinant Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Trans-Activators
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Protein-Tyrosine Kinases