CAML is a p56Lck-interacting protein that is required for thymocyte development

Immunity. 2005 Aug;23(2):139-52. doi: 10.1016/j.immuni.2005.06.006.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Apoptosis / physiology
  • Cell Differentiation* / genetics
  • Cell Differentiation* / immunology
  • Gene Transfer Techniques
  • Humans
  • Jurkat Cells
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology
  • Mice
  • Mice, Knockout
  • Protein Structure, Tertiary
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / physiology
  • Thymus Gland / cytology*
  • Thymus Gland / enzymology*
  • Thymus Gland / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Caml protein, mouse
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)