CAML is required for efficient EGF receptor recycling

David D. Tran, Helen R. Russell, Shari L. Sutor, Jan van Deursen, Richard J. Bram

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Calcium-modulating cyclophilin ligand (CAML) is a ubiquitous protein that has been implicated in signaling from the cell surface receptor TACI in lymphocytes, although its role and mechanism of action are unknown. To study its function in the mouse, we disrupted the CAML gene and found it to be required for early embryonic development, but not for cellular viability. CAML-deficient cells have severely impaired proliferative responses to the epidermal growth factor (EGF). Although EGF-induced activation of signaling intermediates and internalization of the EGF receptor (EGFR) are normal in the absence of CAML, the recycling of internalized receptors to the plasma membrane is defective, leading to its reduced surface accumulation. We demonstrate that CAML normally associates directly with the kinase domain of the EGFR in a ligand-dependent manner. These data implicate CAML in EGFR signaling and suggest that it may play a role in receptor recycling during long-term proliferative responses to EGF.

Original languageEnglish (US)
Pages (from-to)245-256
Number of pages12
JournalDevelopmental Cell
Volume5
Issue number2
DOIs
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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