IQGAP1: insights into the function of a molecular puppeteer.
The intracellular spatiotemporal organization of signaling events is critical for normal cellular function. In response to environmental stimuli, cells utilize highly organized signaling pathways that are subject to multiple layers of regulation. However, the molecular mechanisms that coordinate these complex processes remain an enigma. Scaffolding proteins (scaffolins) have emerged as critical regulators of signaling pathways, many of which have well-described functions in immune cells. IQGAP1, a highly conserved cytoplasmic scaffold protein, is able to curb, compartmentalize, and coordinate multiple signaling pathways in a variety of cell types. IQGAP1 plays a central role in cell-cell interaction, cell adherence, and movement via actin/tubulin-based cytoskeletal reorganization. Evidence also implicates IQGAP1 as an essential regulator of the MAPK and Wnt/β-catenin signaling pathways. Here, we summarize the recent advances on the cellular and molecular biology of IQGAP1. We also describe how this pleiotropic scaffolin acts as a true molecular puppeteer, and highlight the significance of future research regarding the role of IQGAP1 in immune cells.
Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Microbiology & Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Alex M
AM
Abel
Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kristina M
KM
Schuldt
Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kamalakannan
K
Rajasekaran
Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
David
D
Hwang
Department of Microbiology & Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Matthew J
MJ
Riese
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Sridhar
S
Rao
Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Monica S
MS
Thakar
Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Microbiology & Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: subra.malar@bcw.edu.
Subramaniam
S
Malarkannan
D000199:Actins / Q000276:immunology; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D003599:Cytoskeleton / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology*; D014404:Tubulin / Q000276:immunology; D060449:Wnt Signaling Pathway / Q000276:immunology*; D020703:ras GTPase-Activating Proteins / Q000276:immunology*
D000199:Actins; C101203:IQ motif containing GTPase activating protein 1; D014404:Tubulin; D020703:ras GTPase-Activating Proteins
IQGAP1; Lymphocytes; Scaffold proteins; Signaling