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Publication : p21-Activated protein kinases and their emerging roles in glucose homeostasis.

First Author  Chiang YT Year  2014
Journal  Am J Physiol Endocrinol Metab Volume  306
Issue  7 Pages  E707-22
PubMed ID  24368667 Mgi Jnum  J:211477
Mgi Id  MGI:5575567 Doi  10.1152/ajpendo.00506.2013
Citation  Chiang YT, et al. (2014) p21-Activated protein kinases and their emerging roles in glucose homeostasis. Am J Physiol Endocrinol Metab 306(7):E707-22
abstractText  p21-Activated protein kinases (PAKs) are centrally involved in a plethora of cellular processes and functions. Their function as effectors of small GTPases Rac1 and Cdc42 has been extensively studied during the past two decades, particularly in the realms of cell proliferation, apoptosis, and hence tumorigenesis, as well as cytoskeletal remodeling and related cellular events in health and disease. In recent years, a large number of studies have shed light onto the fundamental role of group I PAKs, most notably PAK1, in metabolic homeostasis. In skeletal muscle, PAK1 was shown to mediate the function of insulin on stimulating GLUT4 translocation and glucose uptake, while in pancreatic beta-cells, PAK1 participates in insulin granule localization and vesicle release. Furthermore, we demonstrated that PAK1 mediates the cross talk between insulin and Wnt/beta-catenin signaling pathways and hence regulates gut proglucagon gene expression and the production of the incretin hormone glucagon-like peptide-1 (GLP-1). The utilization of chemical inhibitors of PAK and the characterization of Pak1(-/-) mice enabled us to gain mechanistic insights as well as to assess the overall contribution of PAKs in metabolic homeostasis. This review summarizes our current understanding of PAKs, with an emphasis on the emerging roles of PAK1 in glucose homeostasis.
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