کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2138513 1087878 2007 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evidence of LAT as a dual substrate for Lck and Syk in T lymphocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Evidence of LAT as a dual substrate for Lck and Syk in T lymphocytes
چکیده انگلیسی

LAT is a linker protein essential for activation of T lymphocytes. Its rapid tyrosine-phosphorylation upon T cell receptor (TCR) stimulation recruits downstream signaling molecules for membrane targeting and activation. LAT is physically concentrated in cholesterol-enriched membrane microdomains and is known a substrate for Syk/Zap70 kinase. In this study, we demonstrate that LAT serves as a dual substrate for both Lck and Syk kinases. LAT phosphorylation is absent in Lck-deficient J.CaM1.6 cells and Lck is co-precipitated with LAT in pervanadate-activated Jurkat cells. Further, the in vitro kinase assay using purified Lck and LAT shows that Lck directly phosphorylates LAT. Both Lck and Syk, phosphorylate the ITAM-like motifs on LAT at Y171Y191, which is essential for induction of the interaction of LAT with downstream signaling molecules such as Grb2, PLC-γ1 and c-Cbl, and for activation of MAPK-ERK. Collectively, our data indicate that LAT is an immediate substrate for Lck in one of the earliest events of T cell activation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 31, Issue 4, April 2007, Pages 541–545
نویسندگان
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