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Rho family GTPase signaling through type II p21-activated kinases

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A Correction to this article was published on 25 October 2023

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Abstract

Signaling from the Rho family small GTPases controls a wide range of signaling outcomes. Key among the downstream effectors for many of the Rho GTPases are the p21-activated kinases, or PAK group. The PAK family comprises two types, the type I PAKs (PAK1, 2 and 3) and the type II PAKs (PAK4, 5 and 6), which have distinct structures and mechanisms of regulation. In this review, we discuss signal transduction from Rho GTPases with a focus on the type II PAKs. We discuss the role of PAKs in signal transduction pathways and selectivity of Rho GTPases for PAK family members. We consider the less well studied of the Rho GTPases and their PAK-related signaling. We then discuss the molecular basis for kinase domain recognition of substrates and for regulation of signaling. We conclude with a discussion of the role of PAKs in cross talk between Rho family small GTPases and the roles of PAKs in disease.

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Data Availability Statement

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Change history

Abbreviations

RhoA:

Ras homolog family member A

RAC1:

Ras-related C3 botulinum toxin substrate 1

CDC42:

Cell division control protein 42 homolog

BAD:

Bcl-2-associated agonist of cell death

mDia:

Protein diaphanous homolog

ROCK:

Rho-associated protein kinase

WASP:

Wiskott–Aldrich syndrome protein

N-WASP:

Neural Wiskott–Aldrich syndrome protein

WAVE:

WASP family verprolin-homologous protein

PAK:

P21-activated kinase

Cofilin/ADF:

Cofilin/Actin depolymerizing factor

MRCK:

Myotonic dystrophy kinase-related CDC42-binding kinase

CDC42BPA:

CDC42-binding protein kinase alpha

Par6:

Partitioning defective 6

SSH:

Protein phosphatase Slingshot

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Acknowledgements

We acknowledge Ben Turk and David Calderwood for helpful discussions.

Funding

This work was supported by American Heart Association Grant 961309 and National Institutes of Health Grants R01GM138411 to TJB.

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Authors and Affiliations

  1. Yale College, New Haven, CT, 06520, USA

    Ashwin K. Chetty

  2. Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, CT, 06520, USA

    Ashwin K. Chetty & Titus J. Boggon

  3. Department of Pharmacology, Yale University, 333 Cedar Street, New Haven, CT, 06520, USA

    Byung Hak Ha & Titus J. Boggon

  4. Yale Cancer Center, Yale University, 333 Cedar Street, New Haven, CT, 06520, USA

    Titus J. Boggon

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  1. Ashwin K. Chetty
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Funding: This work was supported by American Heart Association Grant 961309 and National Institutes of Health Grants R01GM138411 to TJB.

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Chetty, A.K., Ha, B.H. & Boggon, T.J. Rho family GTPase signaling through type II p21-activated kinases. Cell. Mol. Life Sci. 79, 598 (2022). https://doi.org/10.1007/s00018-022-04618-2

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  • DOI: https://doi.org/10.1007/s00018-022-04618-2

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