کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9894083 | 1542260 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Role of guanine nucleotide exchange factor P-Rex-2b in sphingosine 1-phosphate-induced Rac1 activation and cell migration in endothelial cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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![عکس صفحه اول مقاله: Role of guanine nucleotide exchange factor P-Rex-2b in sphingosine 1-phosphate-induced Rac1 activation and cell migration in endothelial cells Role of guanine nucleotide exchange factor P-Rex-2b in sphingosine 1-phosphate-induced Rac1 activation and cell migration in endothelial cells](/preview/png/9894083.png)
چکیده انگلیسی
Endothelial cell (EC) migration has an important role in angiogenesis. Sphingosine-1 phosphate (S1P) stimulates EC migration via activation of Gi proteins. In this study, we characterized a mouse guanine nucleotide exchange factor (GEF) P-Rex2b for its regulation by Gβγ and PI3K and its role in S1P-induced Rac1 activation and cell migration in ECs. We found that co-expression of Gβγ or an active form of PI3K (PI3KAC) with P-Rex2b increased the SRE.Luciferase (SRE.L) reporter gene activity that can be stimulated by the Rho family of small GTPases including Rac1. Co-expression with P-Rex2b of Gβγ and PI3KAC or wild type PI3Kγ that can be activated by Gβγ led to further increases in the reporter gene activity. Together with the finding that co-expression of Gβγ and/or PI3KAC increased the levels of active Rac1, we conclude that P-Rex2b is a Rac GEF that can be regulated by Gβγ and PI3K. Additionally, we demonstrated that Gβγ interacted with P-Rex2b, probably through P-Rex2b sequences at the PH domain and that the DEP and PDZ domains of P-Rex2b exerted an inhibitory effect on P-Rex2b's activity because their deletion increased the SER.L reporter gene activity. Furthermore, we found that P-Rex2b is involved in S1P-induced Rac1 activation and cell migration in ECs because siRNA-mediated suppression of P-Rex2b expression in ECs-diminished Rac1 activation and cell migration in response to S1P. Therefore, P-Rex2b is a physiologically significant Rac1 GEF that has an important role in the regulation of EC migration.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Prostaglandins & Other Lipid Mediators - Volume 76, Issues 1â4, May 2005, Pages 95-104
Journal: Prostaglandins & Other Lipid Mediators - Volume 76, Issues 1â4, May 2005, Pages 95-104
نویسندگان
Zhong Li, Jie-Hye Paik, Zhenglong Wang, Tim Hla, Dianqing Wu,