Abstract
A large variety of biological processes is mediated by stimulation of the receptor tyrosine kinase MET. Screening a mouse embryo cDNA library, we were able to identify several novel, putative intracellular TPR/MET-substrates: SNAPIN, DCOHM, VAV-1, Sorting nexin 2, Death associated protein kinase 3, SMC-1, Centromeric protein C, and hTID-1. Interactions as identified by yeast two-hybrid analysis were validated in vitro and in vivo by mammalian two-hybrid studies, a far-western assay and coimmunoprecipitation. Participation in apoptosis-regulating mechanisms through interaction with DAPK-3 and cell cycle control via binding to nuclear proteins such as CENPC and SMC-1 are possible new aspects of intracellular MET signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western / methods
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Embryo, Mammalian / chemistry
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Embryo, Mammalian / metabolism
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Gene Library
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Humans
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Kidney / cytology
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Kidney / embryology
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Mice
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Mutagenesis, Site-Directed / genetics
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Oncogene Proteins, Fusion / chemistry
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Oncogene Proteins, Fusion / metabolism
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Peptides
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Protein Binding
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Protein Interaction Mapping / methods*
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Proto-Oncogene Proteins / chemistry*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-met
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Rats
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Receptors, Growth Factor / chemistry*
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Receptors, Growth Factor / metabolism*
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Sequence Analysis, Protein / methods
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Substrate Specificity
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Two-Hybrid System Techniques
Substances
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Oncogene Proteins, Fusion
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Peptides
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Proto-Oncogene Proteins
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Receptors, Growth Factor
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MET protein, human
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Proto-Oncogene Proteins c-met