G protein coupled receptor transactivation: Extending the paradigm to include serine/threonine kinase receptors

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• 作者：Micah L. Burch^a ; ^b ; Narin Osman^b ; ^c ; Robel Getachew^c ; Sefaa Al-aryahi^c ; Philip Poronnik^c ; Wenhua Zheng^d ; Michael A. Hill^c ; ^e ; Peter J. Little^a ; ^b ; ^c ; ^{peter.little@rmit.edu.au}
• 关键词：G protein coupled receptor ; Serine/threonine protein kinase receptor ; Transactivation ; Vascular smooth muscle ; Proteoglycan
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2012
• 期刊代码：127_13572725
• 类别：med
• 出版时间：May, 2012
• 卷：44
• 期：5
• 页码：722-727
• 文件大小：550 K

摘要

The current paradigm of G protein coupled receptor signaling involves a classical pathway being the activation of phospholipase C and the generation of 1,4,5-inositol trisphosphate, signaling through 尾-arrestin scaffold molecules and the transactivation of tyrosine kinase growth factor receptors. Transactivation greatly expands the range of signaling pathways and responses attributable to the receptor. Recently it has been revealed that G protein coupled receptor agonists can also transactivate the serine/threonine kinase cell surface receptor for transforming growth factor-尾 (Alk5). This leads to the generation of carboxyl terminal phosphorylated Smad2 which is the immediate downstream product of the activated Alk5. Thus, the current paradigm of G protein coupled signaling can be expanded to include the transactivation of the serine kinase receptor Alk5. These insights expand the possibilities for outcomes of therapeutically targeting GPCRs where more substantive and prolonged actions such as the synthesis of extracellular matrix may be affected.