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Gene. 2017 Mar 20;605:20-31. doi: 10.1016/j.gene.2016.12.014. Epub 2016 Dec 19.

Structure, biochemistry, and biology of PAK kinases.

Author information

1
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA; Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India. Electronic address: bcmrxk@gwu.edu.
2
Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India.
3
Department of Cell Biology, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, China Medical University, Shenyang 110122, China.
4
Department of Cell Biology, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, China Medical University, Shenyang 110122, China. Electronic address: fli@mail.cmu.edu.cn.

Abstract

PAKs, p21-activated kinases, play central roles and act as converging junctions for discrete signals elicited on the cell surface and for a number of intracellular signaling cascades. PAKs phosphorylate a vast number of substrates and act by remodeling cytoskeleton, employing scaffolding, and relocating to distinct subcellular compartments. PAKs affect wide range of processes that are crucial to the cell from regulation of cell motility, survival, redox, metabolism, cell cycle, proliferation, transformation, stress, inflammation, to gene expression. Understandably, their dysregulation disrupts cellular homeostasis and severely impacts key cell functions, and many of those are implicated in a number of human diseases including cancers, neurological disorders, and cardiac disorders. Here we provide an overview of the members of the PAK family and their current status. We give special emphasis to PAK1 and PAK4, the prototypes of groups I and II, for their profound roles in cancer, the nervous system, and the heart. We also highlight other family members. We provide our perspective on the current advancements, their growing importance as strategic therapeutic targets, and our vision on the future of PAKs.

KEYWORDS:

Cancer; Cytoskeleton remodeling; Heart; Nervous system; PAK; p21-Activated kinase

PMID:
28007610
PMCID:
PMC5250584
DOI:
10.1016/j.gene.2016.12.014
[Indexed for MEDLINE]
Free PMC Article

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