Vav links the T cell antigen receptor to the actin cytoskeleton and T cell activation independently of intrinsic Guanine nucleotide exchange activity.
著者
和文:
Ana V. Miletic,
Daniel B. Graham,
十川 久美子,
Michio Hiroshima,
Michael J. Hamann,
Saso Cemerski,
Tracie Kloeppel,
Daniel D. Billadeau,
Osami Kanagawa,
徳永 万喜洋,
Wojciech Swat.
英文:
Ana V. Miletic,
Daniel B. Graham,
Kumiko Sakata-Sogawa,
Michio Hiroshima,
Michael J. Hamann,
Saso Cemerski,
Tracie Kloeppel,
Daniel D. Billadeau,
Osami Kanagawa,
Makio Tokunaga,
Wojciech Swat.
言語
English
掲載誌/書名
和文:
英文:
PLoS One
巻, 号, ページ
Vol. 4
No. 8
e6599
出版年月
2009年8月
出版者
和文:
英文:
会議名称
和文:
英文:
開催地
和文:
英文:
アブストラクト
Background: T cell receptor (TCR) engagement leads to formation of signaling microclusters and induction of rapid anddynamic changes in the actin cytoskeleton, although the exact mechanism by which the TCR initiates actin polymerization isincompletely understood. The Vav family of guanine nucleotide exchange factors (GEF) has been implicated in generationof TCR signals and immune synapse formation, however, it is currently not known if Vav’s GEF activity is required in T cellactivation by the TCR in general, and in actin polymerization downstream of the TCR in particular.Methodology/Principal Findings:Here, we report that Vav1 assembles into signaling microclusters at TCR contact sites andis critical for TCR-initiated actin polymerization. Surprisingly, Vav1 functions in TCR signaling and Ca++ mobilization via amechanism that does not appear to strictly depend on the intrinsic GEF activity.Conclusions/Significance:We propose here a model in which Vav functions primarily as a tyrosine phosphorylated linkerproteinfor TCR activation of T cells. Our results indicate that, contrary to expectations based on previously published studiesincluding from our own laboratory, pharmacological inhibition of Vav1’s intrinsic GEF activity may not be an effectivestrategy for T cell-directed immunosuppressive therapy.
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