کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2050744 1074180 2007 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region
چکیده انگلیسی

The juxtamembrane (JM) regions of several receptor tyrosine kinases are involved in autoinhibitory interactions that maintain the low basal activity of the receptors; mutations can give rise to constitutive kinase activity and signaling. In this report, we show that the JM region of the human insulin-like growth factor I receptor (IGF1R) plays a role in kinase regulation. We mutated JM residues that were conserved in this subfamily of receptor tyrosine kinases, and expressed and purified the cytoplasmic domains using the Sf9/baculovirus system. We show that a kinase-proximal mutation (Y957F) and (to a lesser extent) a mutation in the central part of the JM region (N947A) increase the autophosphorylation activity of the kinase. Steady-state kinetic measurements show the mutations cause an increase in Vmax for phosphorylation of peptide substrates. When the holoreceptors were expressed in fibroblasts derived from IGF1R-deficient mice, the Y957F mutation led to a large increase in basal and in IGF1-stimulated receptor autophosphorylation. Together, these data demonstrate that the JM region of IGF1R plays an important role in limiting the basal activity of the receptor.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 581, Issue 17, 10 July 2007, Pages 3235–3240
نویسندگان
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