کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1963795 1058508 2009 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Down-regulating protein kinase C alpha: Functional cooperation between the proteasome and the endocytic system
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Down-regulating protein kinase C alpha: Functional cooperation between the proteasome and the endocytic system
چکیده انگلیسی

Ubiquitination, proteasome, caveolae and endosomes have been implicated in controlling protein kinase Cα (PKCα) down-regulation. However, the molecular mechanism remained obscure. Here we show that endosomes and proteasome cooperate in phorbol ester 12-O-tetradecanoyl phorbol acetate (TPA)-induced down-regulation of PKCα. We show that following TPA treatment and translocation to the plasma membrane, PKCα undergoes multimonoubiquitination prior to its degradation by the proteasome. However, to reach the proteasome, PKCα must travel through the endocytic system from early to late endosomes. This route requires functional endosomes, whereby endosomal alkalinization, or ablation, abrogates completely PKCα degradation maintaining the enzyme at the plasma membrane. This route also depends on synaptotagmin (Syt) II and the Rab7 GTPase, whereby Syt II knock-down or expression of the GDP-locked Rab7 inactive mutant prevents PKCα degradation. We further show that proteasome plays a dual role, where an active proteasome is required for deubiquitination of PKCα, a step crucial to prevent PKCα targeting to the endocytic recycling compartment. Finally, we show that the association with rafts-localized cell surface proteins that internalize in a clathrin-independent fashion is necessary to allow the trafficking of PKCα from the plasma membrane to the proteasome, its ultimate degradation station.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 21, Issue 11, November 2009, Pages 1607–1619
نویسندگان
, ,