T-cell receptor signaling to integrins

Brandon J Burbach, Ricardo B. Medeiros, Kristen L. Mueller, Yoji Shimizu

Research output: Contribution to journalReview articlepeer-review

105 Scopus citations

Abstract

Integrin adhesion receptors are critical for antigen recognition by T cells and for regulated recirculation and trafficking into and through various tissues in the body. T-cell receptor (TCR) signaling induces rapid increases in integrin function that facilitate T-cell activation by promoting stable contact with antigen-presenting cells and extracellular proteins in the environment. In this review, we outline the molecular mechanisms by which the TCR signals to integrins and present a model that highlights four key events: (i) initiation of proximal TCR signals nucleated by the linker for activated T cells (LAT) adapter protein and involving Itk, phospholipase C-γ1, Vav1, and Src homology 2 domain-containing leukocyte-specific phosphoprotein of 76 kDa; (ii) transmission of integrin activation signals from the LAT signalosome to integrins by protein kinase (PK) C and the adapter protein, adhesion and degranulation-promoting adapter protein; (iii) assembly of integrin-associated signaling complexes that include PKD, the guanosine triphosphatase Rap1 and its effectors, and talin; and (iv) reorganization of the actin cytoskeleton by WAVE2 and other actin-remodeling proteins. These events coordinate changes in integrin conformation and clustering that result in enhanced integrin functional activity following TCR stimulation.

Original languageEnglish (US)
Pages (from-to)65-81
Number of pages17
JournalImmunological Reviews
Volume218
Issue number1
DOIs
StatePublished - Aug 2007

Keywords

  • Adapter protein
  • Adhesion
  • Integrin
  • Signal transduction
  • T-cell activation
  • T-cell receptor

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