SCIMP, a transmembrane adaptor protein involved in major histocompatibility complex class II signaling

Mol Cell Biol. 2011 Nov;31(22):4550-62. doi: 10.1128/MCB.05817-11. Epub 2011 Sep 19.

Abstract

Formation of the immunological synapse between an antigen-presenting cell (APC) and a T cell leads to signal generation in both cells involved. In T cells, the lipid raft-associated transmembrane adaptor protein LAT plays a central role. Its phosphorylation is a crucial step in signal propagation, including the calcium response and mitogen-activated protein kinase activation, and largely depends on its association with the SLP76 adaptor protein. Here we report the discovery of a new palmitoylated transmembrane adaptor protein, termed SCIMP. SCIMP is expressed in B cells and other professional APCs and is localized in the immunological synapse due to its association with tetraspanin-enriched microdomains. In B cells, it is constitutively associated with Lyn kinase and becomes tyrosine phosphorylated after major histocompatibility complex type II (MHC-II) stimulation. When phosphorylated, SCIMP binds to the SLP65 adaptor protein and also to the inhibitory kinase Csk. While the association with SLP65 initiates the downstream signaling cascades, Csk binding functions as a negative regulatory loop. The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Antigen Presentation
  • Antigen-Presenting Cells / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CSK Tyrosine-Protein Kinase
  • HEK293 Cells
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunological Synapses / chemistry
  • Lymphocyte Activation
  • Membrane Microdomains / chemistry
  • Membrane Microdomains / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Phosphoproteins / metabolism*
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • src Homology Domains
  • src-Family Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • B cell linker protein
  • Histocompatibility Antigens Class II
  • Membrane Proteins
  • Phosphoproteins
  • RNA, Small Interfering
  • SCIMP protein, human
  • SLP-76 signal Transducing adaptor proteins
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • CSK protein, human
  • Mitogen-Activated Protein Kinases