CAML is required for efficient EGF receptor recycling.
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.
Tran
David D
DD
Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
Russell
Helen R
HR
Sutor
Shari L
SL
van Deursen
Jan
J
Bram
Richard J
RJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C089404:CAMLG protein, human; C490314:Caml protein, mouse; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D011993:Recombinant Fusion Proteins; D012235:Rhodamines; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1