SLAP, a regulator of immunoreceptor ubiquitination, signaling, and trafficking

Immunol Rev. 2009 Nov;232(1):218-28. doi: 10.1111/j.1600-065X.2009.00827.x.

Abstract

Src-like adapter proteins (SLAP and SLAP-2) constitute a family of proteins that are expressed in a variety of cell types but are studied most extensively in lymphocytes. They have been shown to associate with proximal components of the T-cell receptor (TCR) and B-cell receptor (BCR) signaling complexes. An interaction of SLAP with c-Cbl leads to the ubiquitination and degradation of phosphorylated components of the TCR- and BCR-signaling complexes. The absence of this process in immature SLAP-deficient T and B cells leads to increased immunoreceptor levels due to decreased intracellular retention and degradation. We propose a model in which SLAP-dependent regulation of immunoreceptor levels allows for finer control of immunoreceptor signaling. Thus, SLAP functions to dampen immunoreceptor signaling, thereby influencing lymphocyte development and repertoire selection.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / immunology
  • Humans
  • Proto-Oncogene Proteins c-cbl / immunology
  • Proto-Oncogene Proteins c-cbl / metabolism*
  • Proto-Oncogene Proteins pp60(c-src) / immunology
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Receptors, Antigen / immunology
  • Receptors, Antigen / metabolism*
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Ubiquitination / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Receptors, Antigen
  • SLA protein, human
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogene Proteins pp60(c-src)