4.7 Article

The adaptor protein LAD/TSAd mediates laminin-dependent T cell migration via association with the 67 kDa laminin binding protein

Journal

EXPERIMENTAL AND MOLECULAR MEDICINE
Volume 41, Issue 10, Pages 728-736

Publisher

NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2009.41.10.079

Keywords

cell movement; focal adhesion protein-tyrosine kinases; integrins; laminin binding protein 67-kDa, rat; Sh2d2a protein, mouse

Funding

  1. Korea research foundation grant [KRF-2006-C00308]
  2. Molecular and Cellular Biodiscovery Program [M1-06N0100-16210]
  3. Korea Science and Engineering Foundation [2006-08367]
  4. National Research Foundation of Korea [2006-08367] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The adaptor protein, LAD/TSAd, plays essential roles in T cell activation. To further understand the functions of this protein, we performed yeast two-hybrid screening using TSAd as bait and identified 67 kDa laminin binding protein (LBP) as the interacting partner. Subsequently, TSAd-LBP interaction was confirmed in D1.1 T cell line. Upon costimulation by T cell receptor (TCR) plus laminin crosslinking or TCR plus integrin alpha 6 crosslinking, LBP was coimmunoprecipitated with TSAd. Moreover, TCR plus laminin costimulation-dependent T cell migration was enhanced in D1.1 T cells overexpressing TSAd but was disrupted in D1.1 cells overexpressing dominant negative form of TSAd or TSAd shRNA. These data show that, upon TCR plus integrin costimulation, TSAd associates with LBP and mediates T lymphocyte migration.

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