IQGAP1 and its binding proteins control diverse biological functions

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.

Figure 1. A schematic diagram of IQGAP1 showing the regions of interaction of its binding partners

A, Established binding partners. B, Binding partners identified since 2006. Only proteins that have been documented to bind IQGAP1 in vitro are shown. CHD, calponin homology domain; WW, polyproline binding region; IQ, IQ domain containing four IQ motifs; GRD, Ras GTPase-activating protein-related domain; RGCT, RasGAP C-terminus. Numbers indicate amino acid residues taken from Pfam database (http://www.sanger.ac.uk/resources/databases/pfam.html).

Figure 1. A schematic diagram of IQGAP1 showing the regions of interaction of its binding partners

A, Established binding partners. B, Binding partners identified since 2006. Only proteins that have been documented to bind IQGAP1 in vitro are shown. CHD, calponin homology domain; WW, polyproline binding region; IQ, IQ domain containing four IQ motifs; GRD, Ras GTPase-activating protein-related domain; RGCT, RasGAP C-terminus. Numbers indicate amino acid residues taken from Pfam database (http://www.sanger.ac.uk/resources/databases/pfam.html).