Abstract
The adapter protein Crk contains an SH2 domain and two SH3 domains. Through binding of particular ligands to the SH2 domain and the N-terminal SH3 domain, Crk has been implicated in a number of signaling processes, including regulation of cell growth, cell motility, and apoptosis. We report here that the C-terminal SH3 domain, never shown to bind any specific signaling molecules, contains a binding site for the nuclear export factor Crm1. We find that a mutant Crk protein, deficient in Crm1 binding, promotes apoptosis. Moreover, this nuclear export sequence mutant [NES(-) Crk] interacts strongly, through its SH2 domain, with the nuclear tyrosine kinase, Wee1. Collectively, these data suggest that a nuclear population of Crk bound to Wee1 promotes apoptotic death of mammalian cells.
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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Active Transport, Cell Nucleus
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Apoptosis / physiology*
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Cell Compartmentation
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Cell Cycle Proteins*
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Cell Nucleus / physiology
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Exportin 1 Protein
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Humans
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Karyopherins / metabolism*
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Male
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Mutation
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Nuclear Proteins*
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Protein Binding
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Protein Sorting Signals
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins c-crk
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Proto-Oncogene Proteins*
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Receptors, Cytoplasmic and Nuclear*
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Signal Transduction
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src Homology Domains
Substances
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Cell Cycle Proteins
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Karyopherins
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Nuclear Proteins
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Protein Sorting Signals
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-crk
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Receptors, Cytoplasmic and Nuclear
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Protein Kinases
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Protein-Tyrosine Kinases
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WEE1 protein, human