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Role of p21-activated kinases in cardiovascular development and function

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Abstract

p21-activated kinases (Paks) are a group of six serine/threonine kinases (Pak1-6) that are involved in a variety of biological processes. Recently, Paks, more specifically Pak1, -2, and -4, have been shown to play important roles in cardiovascular development and function in a range of model organisms including zebrafish and mice. These functions include proper morphogenesis and conductance of the heart, cardiac contractility, and development and integrity of the vasculature. The mechanisms underlying these effects are not fully known, but they likely differ among the various Pak isoforms and include both kinase-dependent and -independent functions. In this review, we discuss aspects of Pak function relevant to cardiovascular biology as well as potential therapeutic implications of small-molecule Pak inhibitors in cardiovascular disease.

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Abbreviations

ANP:

Atrial natriuretic peptide

Cko:

Conditional knock-out

Erk:

Extracellular-regulated kinase

GAP:

Guanine-nucleotide activating proteins

GDI:

Guanine-nucleotide dissociation inhibitor

GEF:

Guanine-nucleotide exchange factor

LIMK:

LIM kinase

MAPK:

Mitogen-activated protein kinase

MLC:

Myosin light chain

Pak:

p21-Activated kinase

PDK:

Phosphoinositide-dependent kinase

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Authors and Affiliations

  1. Department of Biochemistry, Drexel University School of Medicine, Philadelphia, PA, USA

    Mollie L. Kelly & Jonathan Chernoff

  2. Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA

    Mollie L. Kelly & Artyom Astsaturov

Authors
  1. Mollie L. Kelly
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  2. Artyom Astsaturov
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  3. Jonathan Chernoff
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Correspondence to Jonathan Chernoff.

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Kelly, M.L., Astsaturov, A. & Chernoff, J. Role of p21-activated kinases in cardiovascular development and function. Cell. Mol. Life Sci. 70, 4223–4228 (2013). https://doi.org/10.1007/s00018-013-1347-8

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  • DOI: https://doi.org/10.1007/s00018-013-1347-8

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