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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5122-5128. Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2005-10-061838. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-10-061838v1 109/12/5122    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Park, D. Articles by Yun, Y. Search for Related Content PubMed PubMed Citation Articles by Park, D. Articles by Yun, Y. Related Collections Cell Adhesion and Motility Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS The adaptor protein Lad associates with the G protein ß subunit and mediates chemokine-dependent T-cell migration Dongsu Park1, Inyoung Park1, Deogwon Lee1, Young Bong Choi1, Hyunsook Lee2, and Yungdae Yun1 1 Department of Life Science, Ewha Woman's University, Seoul, Korea; and 2 Department of Biological Science, Seoul National University, Seoul, Korea Lck-interacting adaptor protein/Rlk/Itk-binding protein (Lad/RIBP) was previously identified as an adaptor protein involved in TCR-mediated T-cell activation. To elucidate the functions of Lad further, we here performed yeast 2-hybrid screening using Lad as bait and discovered that the G protein ß subunit (Gß) is a Lad-binding partner. Since the most well-known G protein–coupled receptor in T cells is the chemokine receptor, we investigated whether Lad is involved in chemokine signaling. We found that, upon chemokine treatment, Lad associated with Gß in Jurkat T cells. Furthermore, ectopic expression of dominant-negative Lad or the reduction of endogenous Lad expression by siRNA impaired the chemokine-induced migration of T cells, indicating that Lad is required for chemokine-induced T-cell migration. Subsequent investigation of the signaling pathways revealed that, in response to chemokine, Lad associated with the tyrosine kinases Lck and Zap-70 and that Lad was essential for the activation of Zap-70. Moreover, Lad was required for the chemokine-dependent tyrosine phosphorylation of focal adhesion molecules that included Pyk2 and paxillin. Taken together, these data show that, upon chemokine stimulation, Lad acts as an adaptor protein that links the G protein ß subunit to the tyrosine kinases Lck and Zap-70, thereby mediating T-cell migration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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