CAML is a p56Lck-interacting protein that is required for thymocyte development.
Calcium modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein implicated in T cell signaling, although its mechanism and physiologic role in the immune system are unknown. We show here that CAML is essential for peripheral T cell development. Inactivation of CAML in mouse thymocytes lowered the numbers of double-positive and single-positive thymocytes, concomitant with reduced positive and enhanced negative selection. We found that CAML interacts with p56Lck and appears to regulate subcellular localization of the kinase in both resting and T cell receptor (TCR)-stimulated cells. CAML-deficient cells displayed enhanced p56lck and ZAP-70 phosphorylation and increased IL2 production and cell death after TCR stimulation, suggesting that CAML may act as a negative regulator of p56lck. Our data establish a novel role for CAML as an essential mediator of T cell survival during thymopoiesis and indicate that its loss deregulates p56Lck signaling.
Tran
David D
DD
Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Edgar
Contessa E
CE
Heckman
Karin L
KL
Sutor
Shari L
SL
Huntoon
Catherine J
CJ
van Deursen
Jan
J
McKean
David L
DL
Bram
Richard J
RJ
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D018014:Gene Transfer Techniques; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C490314:Caml protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)