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Classical Rho Proteins: Biochemistry of Molecular Switch Function and Regulation

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Ras Superfamily Small G Proteins: Biology and Mechanisms 1

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Abstract

Rho family proteins are involved in an array of cellular processes by modulating cytoskeletal organization, transcription, and cell cycle progression. The signaling functions of Rho family proteins are based on the formation of distinctive protein–protein complexes with their regulators and effectors. A necessary precondition for such differential interactions is an intact molecular switch function, which is a hallmark of most members of the Rho family. Such classical Rho proteins cycle between an inactive GDP-bound state and an active GTP-bound state. They specifically interact via a consensus-binding sites called switch I and II with three structurally and functionally unrelated classes of regulatory proteins, such as guanine nucleotide dissociation inhibitors (GDIs), guanine nucleotide exchange factors (GEFs), and GTPase-activating proteins (GAPs). Extensive studies in the last 25 years have provided invaluable insights into the molecular mechanisms underlying regulation and signal transduction of the Rho family proteins. In this chapter, we will review common features of Rho protein regulations and highlight specific aspects of their structure–function relationships.

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Abbreviations

A:

Aliphatic amino acid

Bcr:

Breakpoint cluster region protein

C:

Cysteine

CZH:

CDM-zizimin homology

Db1:

Diffuse B-cell lymphoma

DH:

Dbl homology domain

DHR1&2:

DOCK-homology regions 1 and 2

ERM:

Ezrin/radixin/moesin

GAPs:

GTPase-activating proteins

GDIs:

Guanine nucleotide dissociation inhibitors

GDP:

Guanosine diphosphate

GEFs:

Guanine nucleotide exchange factors

Gln:

Glutamine

Gly:

Glycine

GTP:

Guanosine triphosphate

p75NTR :

Neurotrophin receptor p75

PAK1:

p21-activated kinase 1

PH:

Pleckstrin homology domain

PKA:

Protein kinase A

PKC:

Protein kinase C

P-loop:

Phosphate-binding loop

X:

Any amino acid

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Authors and Affiliations

  1. Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, 40225, Düsseldorf, Germany

    Si-Cai Zhang, Kazem Nouri, Ehsan Amin, Mohamed S. Taha, Hossein Nakhaeizadeh, Saeideh Nakhaei-Rad, Radovan Dvorsky & Mohammad Reza Ahmadian

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    Alfred Wittinghofer

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Zhang, SC. et al. (2014). Classical Rho Proteins: Biochemistry of Molecular Switch Function and Regulation. In: Wittinghofer, A. (eds) Ras Superfamily Small G Proteins: Biology and Mechanisms 1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1806-1_14

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