IQGAP Family Members in Yeast, Dictyostelium, and Mammalian Cells - PubMed (original) (raw)

IQGAP Family Members in Yeast, Dictyostelium, and Mammalian Cells

Katie B Shannon. Int J Cell Biol. 2012.

Abstract

IQGAPs are a family of scaffolding proteins with multiple domains, named for the IQ motifs and GTPase activating protein (GAP) related domains. Despite their GAP homology, IQGAP proteins act as effectors for GTP-bound GTPases of the Ras superfamily and do not stimulate GTP hydrolysis. IQGAPs are found in eukaryotic cells from yeast to human, and localize to actin-containing structures such as lamellipodia, membrane ruffles, cell-cell adhesions, phagocytic cups, and the actomyosin ring formed during cytokinesis. Mammalian IQGAPs also act as scaffolds for signaling pathways. IQGAPs perform their myriad functions through association with a large number of proteins including filamentous actin (F-actin), GTPases, calcium-binding proteins, microtubule binding proteins, kinases, and receptors. The focus of this paper is on recent studies describing new binding partners, mechanisms of regulation, and biochemical and physiological functions of IQGAPs in yeast, amoeba, and mammalian cells.

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Figures

Figure 1

Figure 1

IQGAP domain structure in yeasts, Dictyostelium discoideum, and mammalian cells. Domain boundaries were determined by MotifScan using Prosite and Pfam sources [2]. (a) IQGAP family members from yeast. The most related members are AgCyk1 31% identical to ScIqg1, CaIqg1 20% identical to ScIqg1 and 24% identical to SpRng2. Note that additional IQ motifs were identified in CaIqg1 and ScIqg1 by visual scanning [3]. (b) IQGAP family members characterized in Dictyostelium discoideum. Percent identify at the amino acid level is shown for each pair. (c) Human IQGAP family members. CHD-calponin homology domain, IR-internal repeats (coiled-coil region), WW-tryptophan containing repeats, IQ-isoleucine and glutamine rich repeats, GRD-GAP-related domain, RGCt-Ras GAP C-terminus homology domain NLS, nuclear localization sequence. Note that not all members of the family contain each domain found in IQGAP1. Although WW domains of other proteins have been shown to bind to proline-rich proteins [4], no such interactions have yet been described for IQGAPs.

Figure 2

Figure 2

Amino acid sequence alignment of the N-terminus from S. pombe (SpRng2), C. albicans (CaIqg1) and S. cerevisiae (ScIqg1). Amino acids 1–300 of Rng2, which were identified as important for F-actin nucleation activity of Rng2 in vitro, were aligned with the N-terminal 490 amino acids of CaIqg1 and 420 amino acids of ScIqg1 using Clustal 2.1 multiple sequence alignment default settings at

http://www.ebi.ac.uk/Tools/msa/clustalw2/

. Amino acids highlighted in yellow were identified as phosphorylation sites by mass spec analysis, doubly underlined amino acids represent consensus CDK sites (S/TPxK), amino acids highlighted blue are the CHD, ScIqg1 amino acids highlighted in red are the APC/C recognition site, and Rng2 amino acids highlighted green are those identified as being important for F-actin nucleation activity.

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