Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesion

Lisa D. Finkelstein, Yoji Shimizu, Pamela L. Schwartzberg

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

T cells deficient in the Tec kinases Itk or Itk and Rlk exhibit defective TCR-stimulated proliferation, IL-2 production, and activation of phospholipase C-γ. Evidence also implicates Tec kinases in actin cytoskeleton regulation, which is necessary for cell adhesion and formation of the immune synapse in T lymphocytes. In this study we show that Tec kinases are required for TCR-mediated up-regulation of adhesion via the LFA-1 integrin. We also demonstrate that the defect in adhesion is associated with defective clustering of LFA-1 and talin at the site of interaction of Rlk-/-Itk -/- and Itk-/- T cells with anti-TCR-coated beads. Defective recruitment of Vav1, protein kinase Cθ, and Pyk2 was also observed in Rlk-/-Itk-/- and Itk-/- T cells. Stimulation with ICAM-2 in conjunction with anti-TCR-coated beads enhanced polarization of Vav1, protein kinase Cθ, and Pyk2 in wild-type cells, demonstrating a role for integrins in potentiating the recruitment of signaling molecules in T cells. Increased recruitment of signaling molecules was most pronounced under conditions of low TCR stimulation. Under these suboptimal TCR stimulation conditions, ICAM-2 could also enhance the recruitment of signaling molecules in Itk-/-, but not Rlk-/-Itk-/- T cells. Thus, Tec kinases play key roles in regulating TCR-mediated polarization of integrins and signaling molecules to the site of TCR stimulation as well as the up-regulation of integrin adhesion.

Original languageEnglish (US)
Pages (from-to)5923-5930
Number of pages8
JournalJournal of Immunology
Volume175
Issue number9
DOIs
StatePublished - Nov 1 2005

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Cell Adhesion
Integrins
T-Lymphocytes
Lymphocyte Function-Associated Antigen-1
Protein Kinase C
Up-Regulation
Talin
Type C Phospholipases
Actin Cytoskeleton
Synapses
Interleukin-2
Cluster Analysis
Tec protein-tyrosine kinase

Cite this

Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesion. / Finkelstein, Lisa D.; Shimizu, Yoji; Schwartzberg, Pamela L.

In: Journal of Immunology, Vol. 175, No. 9, 01.11.2005, p. 5923-5930.

Research output: Contribution to journalArticle

Finkelstein, Lisa D. ; Shimizu, Yoji ; Schwartzberg, Pamela L. / Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesion. In: Journal of Immunology. 2005 ; Vol. 175, No. 9. pp. 5923-5930.
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