Elsevier

Cellular Signalling

Volume 24, Issue 4, April 2012, Pages 826-834
Cellular Signalling

Review
IQGAP1 and its binding proteins control diverse biological functions

https://doi.org/10.1016/j.cellsig.2011.12.005Get rights and content

Abstract

IQGAP proteins have been identified in a wide spectrum of organisms, ranging from yeast to humans. The most extensively studied family member is the ubiquitously expressed scaffold protein IQGAP1, which participates in multiple essential aspects of mammalian biology. IQGAP1 mediates these effects by binding to and regulating the function of numerous interacting proteins. Over ninety proteins have been reported to associate with IQGAP1, either directly or as part of a larger complex. In this review, we summarise those IQGAP1 binding partners that have been identified in the last five years. The molecular mechanisms by which these interactions contribute to the functions of receptors and their signalling cascades, small GTPase function, cytoskeletal dynamics, neuronal regulation and intracellular trafficking are evaluated. The evidence that has accumulated recently validates the role of IQGAP1 as a scaffold protein and expands the repertoire of cellular activities in which it participates.

Highlights

► IQGAP proteins have been identified in a wide spectrum of organisms. ► The most extensively studied family member is IQGAP1. ► Over ninety proteins have been reported to associate with IQGAP1. ► Here, we summarise those IQGAP1 binding partners identified in the last five years.

Introduction

The IQGAP family of proteins is found in numerous organisms, including yeast, fish, Xenopus and mammals. Three IQGAP proteins, termed IQGAP1, IQGAP2 and IQGAP3, have been identified in humans. IQGAP1 was first described in 1994 [1], followed two years later by IQGAP2 [2], while IQGAP3 was isolated in 2007 [3]. The IQGAPs exhibit some common characteristics, including considerable sequence overlap. Nevertheless, they differ in many aspects, such as function, tissue distribution and subcellular localization. For example, IQGAP1 is ubiquitously expressed, while IQGAP2 is found predominantly in the liver and IQGAP3 expression appears confined to the brain, lung, testis, small intestine and colon [3].

Published studies from many investigators have identified roles for IQGAP1 in diverse aspects of mammalian biology. These range from regulation of the cytoskeleton and cell migration to participation in cancer and microbial infection. These topics have been covered in several excellent reviews [4], [5], [6], [7], [8], [9]. Here, we focus on studies published since 2006 in which previously unrecognised binding partners of IQGAP1 were identified.

Section snippets

IQGAP1 binding partners

IQGAP1 is the best characterised of the IQGAP proteins. Relatively little is known about the spectrum of binding interactions of IQGAP2 and IQGAP3. By contrast, the number of proteins known to bind IQGAP1 has more than doubled since the publication in 2006 of the last major review article addressing this topic [10]. Over ninety proteins have been reported to bind IQGAP1. These proteins have been found either by investigators looking for unidentified IQGAP1 binding partners (e.g., CLIP-170 [11],

Perspectives

Accumulated evidence reinforces the concept that IQGAP1 acts as a scaffold protein, integrating multiple signalling pathways and coordinating cellular activities. In addition, the functions of several IQGAP1 binding interactions remain completely unknown (Table 1), implying that IQGAP1 may be involved in other biological processes. For example, analogous to the MAPK cascade, IQGAP1 associates with several components of the PI3K/Akt pathway [47], [51], [54], [98], [99]. Scaffold proteins such as

Acknowledgements

The authors apologise to all whose primary work could not be cited owing to space restrictions. This work was supported in part by the Department of Defense Breast Cancer Research Programme (to C.D.W.) and by the Intramural Research Programme of the US National Institutes of Health.

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