کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1963765 1058498 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A negative regulatory role for Y1111 on the Tie-2 RTK
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A negative regulatory role for Y1111 on the Tie-2 RTK
چکیده انگلیسی

Tie2 is a receptor tyrosine kinase (RTK) essential for aspects of both normal and pathological angiogenesis. Understanding how this receptor is regulated is important for development of therapeutic angiogenic agents. Evidence suggests the C-terminal tail of the receptor plays a negative regulatory role in Tie2 signaling and function. Here we investigated the role of a specific C-tail residue, Y1111, in Tie2 signaling by generating a number of receptor point mutants. We found that mutation of this site to phenylalanine (Y1111F) results in an increase in receptor phosphorylation and kinase activity, as well as increased downstream signaling. Furthermore, mutation of Y1111 to the highly charged aspartate (Y1111D) or glutamate (Y1111E) results in even more dramatic increase in receptor phosphorylation and activity. Limited protease digestion studies indicate that these mutations may alter receptor conformation and potentially relieve negative inhibition imparted by the C-tail of Tie2. These studies suggest that Y1111 plays a key role in negative regulation of Tie2 activity and they provide important insight into molecular mechanisms behind the intrinsic ability of this RTK to regulate its own activity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 22, Issue 4, April 2010, Pages 676–683
نویسندگان
, , , ,