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The adaptor protein Lad associates with the G protein β subunit and mediates chemokine-dependent T-cell migration
- The adaptor protein Lad associates with the G protein β subunit and mediates chemokine-dependent T-cell migration
- Park D.; Park I.; Lee D.; Young B.C.; Lee H.; Yun Y.
- Ewha Authors
- 윤영대; 박인영
- SCOPUS Author ID
- 윤영대; 박인영
- Issue Date
- Journal Title
- Blood vol. 109, no. 12, pp. 5122 - 5128
- SCIE; SCOPUS
- Document Type
- 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 β subunit (Gβ) 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 Gβ 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 β subunit to the tyrosine kinases Lck and Zap-70, thereby mediating T-cell migration. © 2007 by The American Society of Hematology.
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