Structure, biochemistry, and biology of PAK kinases

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 reloca...

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Bibliographic Details
Published inGene Vol. 605; pp. 20 - 31
Main Authors Kumar, Rakesh, Sanawar, Rahul, Li, Xiaodong, Li, Feng
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 20.03.2017
Subjects
Alternative Splicing
Cancer
Cardiovascular Diseases - enzymology
Cardiovascular Diseases - genetics
Cardiovascular Diseases - pathology
cell cycle
cell movement
cytoskeleton
Cytoskeleton - chemistry
Cytoskeleton - metabolism
Cytoskeleton - ultrastructure
Cytoskeleton remodeling
gene expression
Heart
homeostasis
human diseases
Humans
inflammation
metabolism
Myocardium - enzymology
Myocardium - pathology
neoplasms
Neoplasms - enzymology
Neoplasms - genetics
Neoplasms - pathology
Nervous system
Nervous System - enzymology
Nervous System - pathology
nervous system diseases
Nervous System Diseases - enzymology
Nervous System Diseases - genetics
Nervous System Diseases - pathology
p21-Activated kinase
p21-Activated Kinases - chemistry
p21-Activated Kinases - genetics
p21-Activated Kinases - metabolism
PAK
Phosphorylation
phosphotransferases (kinases)
Protein Domains
Protein Transport
prototypes
Signal Transduction
Substrate Specificity
Heart
PBD
Cytoskeleton remodeling
Nervous system
PAK
AID
p21-Activated kinase
Cancer
Online AccessGet full text
ISSN0378-1119
1879-0038
1879-0038
DOI10.1016/j.gene.2016.12.014

Cover

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. •PAKs act as modifiers of the cell surface and intracellular signaling cascades.•PAKs function both in the cytoplasm and nucleus and regulation of gene expression.•Relevance of PAKs ranges from cellular homeostasis to pathobiology of human disease.•PAKs are dysregulated in cancer, and neurological, cardiac and other disorders.•Modifying PAK activity has emerged as a therapeutic approach for many disorders.
AbstractList 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.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.
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. •PAKs act as modifiers of the cell surface and intracellular signaling cascades.•PAKs function both in the cytoplasm and nucleus and regulation of gene expression.•Relevance of PAKs ranges from cellular homeostasis to pathobiology of human disease.•PAKs are dysregulated in cancer, and neurological, cardiac and other disorders.•Modifying PAK activity has emerged as a therapeutic approach for many disorders.
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.
Author Li, Feng
Li, Xiaodong
Kumar, Rakesh
Sanawar, Rahul
AuthorAffiliation b Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India
c Department of Cell Biology, Key laboratory of Medical Cell Biology, Chinese Ministry of Education, China Medical University, Shenyang, 110122, China
a Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA
AuthorAffiliation_xml – name: b Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India
– name: c Department of Cell Biology, Key laboratory of Medical Cell Biology, Chinese Ministry of Education, China Medical University, Shenyang, 110122, China
– name: a Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA
Author_xml – sequence: 1
  givenname: Rakesh
  surname: Kumar
  fullname: Kumar, Rakesh
  email: bcmrxk@gwu.edu
  organization: Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA
– sequence: 2
  givenname: Rahul
  surname: Sanawar
  fullname: Sanawar, Rahul
  organization: Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India
– sequence: 3
  givenname: Xiaodong
  surname: Li
  fullname: Li, Xiaodong
  organization: Department of Cell Biology, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, China Medical University, Shenyang 110122, China
– sequence: 4
  givenname: Feng
  surname: Li
  fullname: Li, Feng
  email: fli@mail.cmu.edu.cn
  organization: Department of Cell Biology, Key Laboratory of Medical Cell Biology, Chinese Ministry of Education, China Medical University, Shenyang 110122, China
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28007610$$D View this record in MEDLINE/PubMed
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Cancer
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Snippet 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...
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SubjectTerms Alternative Splicing
Cancer
Cardiovascular Diseases - enzymology
Cardiovascular Diseases - genetics
Cardiovascular Diseases - pathology
cell cycle
cell movement
cytoskeleton
Cytoskeleton - chemistry
Cytoskeleton - metabolism
Cytoskeleton - ultrastructure
Cytoskeleton remodeling
gene expression
Heart
homeostasis
human diseases
Humans
inflammation
metabolism
Myocardium - enzymology
Myocardium - pathology
neoplasms
Neoplasms - enzymology
Neoplasms - genetics
Neoplasms - pathology
Nervous system
Nervous System - enzymology
Nervous System - pathology
nervous system diseases
Nervous System Diseases - enzymology
Nervous System Diseases - genetics
Nervous System Diseases - pathology
p21-Activated kinase
p21-Activated Kinases - chemistry
p21-Activated Kinases - genetics
p21-Activated Kinases - metabolism
PAK
Phosphorylation
phosphotransferases (kinases)
Protein Domains
Protein Transport
prototypes
Signal Transduction
Substrate Specificity
Title Structure, biochemistry, and biology of PAK kinases
URI https://dx.doi.org/10.1016/j.gene.2016.12.014
https://www.ncbi.nlm.nih.gov/pubmed/28007610
https://www.proquest.com/docview/1852782179
https://www.proquest.com/docview/2000480622
https://pubmed.ncbi.nlm.nih.gov/PMC5250584
Volume 605
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