Apoptotic regulation by the Crk adapter protein mediated by interactions with Wee1 and Crm1/exportin.
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.
Mesh Terms:
Active Transport, Cell Nucleus, Apoptosis, Cell Compartmentation, Cell Cycle Proteins, Cell Nucleus, Humans, Karyopherins, Male, Mutation, Nuclear Proteins, Protein Binding, Protein Kinases, Protein Sorting Signals, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-crk, Receptors, Cytoplasmic and Nuclear, Signal Transduction, src Homology Domains
Active Transport, Cell Nucleus, Apoptosis, Cell Compartmentation, Cell Cycle Proteins, Cell Nucleus, Humans, Karyopherins, Male, Mutation, Nuclear Proteins, Protein Binding, Protein Kinases, Protein Sorting Signals, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-crk, Receptors, Cytoplasmic and Nuclear, Signal Transduction, src Homology Domains
Mol. Cell. Biol.
Date: Mar. 01, 2002
PubMed ID: 11839808
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