دورية أكاديمية
Protein kinase CK2 phosphorylates and activates p21-activated kinase 1
| العنوان: | Protein kinase CK2 phosphorylates and activates p21-activated kinase 1 |
|---|---|
| المؤلفون: | Shin, Yong Jae, Kim, Yong-Bae, Kim, Jeong-Ho |
| المصدر: | Biochemistry and Molecular Medicine Faculty Publications |
| بيانات النشر: | Health Sciences Research Commons |
| سنة النشر: | 2013 |
| المجموعة: | George Washington University: Health Sciences Research Commons (HSRC) |
| مصطلحات موضوعية: | PAK1, CK2, Cancer, Casein Kinase II--metabolism, p21-Activated Kinases--metabolism, Cancer Biology, Cell Biology |
| الوصف: | Activation of the p21-activated kinase 1 (PAK1) is achieved through a conformational change that converts an inactive PAK1 dimer to an active monomer. In this paper, we show that this change is necessary but not sufficient to activate PAK1 and that it is, rather, required for CK2-dependent PAK1S223 phosphorylation that converts a monomeric PAK1 into a catalytically active form. This phosphorylation appears to be essential for autophosphorylation at specific residues and overall activity of PAK1. A phosphomimetic mutation (S223E) bypasses the requirement for GTPases in PAK1 activation, whereas the constitutive activity of the PAK1 mutant (PAK1H83,86L), postulated to mimic GTPase-induced structural changes, is abolished by inhibition of S223 phosphorylation. Thus, S223 is likely accessible to CK2 upon conformational changes of PAK1 induced by GTPase-dependent and GTPase-independent stimuli, suggesting that S223 phosphorylation may play a key role in the final step of the PAK1 activation process. The physiological significance of this phosphorylation is reinforced by the observations that CK2 is responsible for epidermal growth factor–induced PAK1 activation and that inhibition of S223 phosphorylation abrogates PAK1-mediated malignant transformation of prostate epithelial cells. Taken together, these findings identify CK2 as an upstream activating kinase of PAK1, providing a novel mechanism for PAK1 activation. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/102Test; https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=1102&context=smhs_biochem_facpubsTest |
| الإتاحة: | https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/102Test https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=1102&context=smhs_biochem_facpubsTest |
| رقم الانضمام: | edsbas.5384A0BC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |