Apoptotic regulation by the Crk adapter protein mediated by interactions with Wee1 and Crm1/exportin.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Smith, JJ; Richardson, DA; Kopf, J; Yoshida, M; Hollingsworth, RE; Kornbluth, S

Published Date

  • March 2002

Published In

Volume / Issue

  • 22 / 5

Start / End Page

  • 1412 - 1423

PubMed ID

  • 11839808

Pubmed Central ID

  • 11839808

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.22.5.1412-1423.2002


  • eng