Abstract
STAM containing an SH3 (Src homology 3) domain and an immunoreceptor tyrosine-based activation motif was previously revealed to be implicated in signaling pathways immediately downstream of Jak2 and Jak3 tyrosine kinases associated with cytokine receptors. We molecularly cloned a novel molecule interacting with the SH3 domain of STAM, which was named AMSH (associated molecule with the SH3 domain of STAM). AMSH contains a putative bipartite nuclear localization signal and a homologous region of a c-Jun activation domain-binding protein 1 (JAB1) subdomain in addition to a binding site for the SH3 domain of STAM. AMSH mutant deleted of the C-terminal half conferred dominant negative effects on signaling for DNA synthesis and c-myc induction mediated by interleukin 2 and granulocyte macrophage-colony-stimulating factor. These results suggest that AMSH plays a critical role in the cytokine-mediated intracellular signal transduction downstream of the Jak2/Jak3.STAM complex.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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COP9 Signalosome Complex
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cloning, Molecular
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Consensus Sequence
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DNA Replication
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DNA-Binding Proteins / metabolism
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Endosomal Sorting Complexes Required for Transport
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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In Situ Hybridization, Fluorescence
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Interleukin-2 / metabolism
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Intracellular Signaling Peptides and Proteins
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Peptide Hydrolases
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Phosphoproteins / metabolism*
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Proto-Oncogene Proteins c-myc / metabolism
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Signal Transduction*
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Transcription Factors / metabolism
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src Homology Domains*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA-Binding Proteins
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Endosomal Sorting Complexes Required for Transport
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Interleukin-2
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Intracellular Signaling Peptides and Proteins
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Phosphoproteins
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Proto-Oncogene Proteins c-myc
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STAM protein, human
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Transcription Factors
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Granulocyte-Macrophage Colony-Stimulating Factor
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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Peptide Hydrolases
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COPS5 protein, human
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COP9 Signalosome Complex