The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling

Abstract

The scaffold protein IQGAP1 assembles multiprotein signaling complexes to influence biological functions. Cell surface receptors, particularly receptor tyrosine kinases and G-protein coupled receptors, are common IQGAP1 binding partners. Interactions with IQGAP1 modulate receptor expression, activation, and/or trafficking. Moreover, IQGAP1 couples extracellular stimuli to intracellular outcomes via scaffolding of signaling proteins downstream of activated receptors, including mitogen-activated protein kinases, constituents of the phosphatidylinositol 3-kinase pathway, small GTPases, and β-arrestins. Reciprocally, some receptors influence IQGAP1 expression, subcellular localization, binding properties, and post-translational modifications. Importantly, the receptor:IQGAP1 crosstalk has pathological implications ranging from diabetes and macular degeneration to carcinogenesis. Here, we describe the interactions of IQGAP1 with receptors, summarize how they modulate signaling, and discuss their contribution to pathology. We also address the emerging functions in receptor signaling of IQGAP2 and IQGAP3, the other human IQGAP proteins. Overall, this review emphasizes the fundamental roles of IQGAPs in coupling activated receptors to cellular homeostasis.

Identification and validation of non‐coding RNA‐mediated high expression of IQGAP3 in poor prognosis of lung adenocarcinoma

“…The IQGAP family includes three members: IQGAP1, IQGAP2 and IQGAP3. 5 IQGAP3 was previously proved to be an oncogene and correlates with poor cancer prognosis. 6 IQGAP3 was also determined to be highly expressed in many cancers, including colorectal cancer, breast cancer and hepatocellular carcinoma.…”

IQGAP3 Is an Important Mediator of Skin Inflammatory Diseases

“…The IQGAP family of scaffold proteins mediate various signaling pathways, including EGFR and WNT pathways, CXCR2 and CXCR4 signaling, IFN and NFkB signaling, the cascades of cytoskeletal organization, cell adhesion and migration [7,8] Most of the aforementioned pathways play roles in the development of psoriatic plaques. Additionally, a hallmark of psoriasis is hyperkeratosis arising due to the hyperproliferation of keratinocytes, and different researchers have shown partial knockdown of IQGAP proteins to decrease the growth and proliferation rates and migration capacity of various types of cells-skin cells [9], liver cells [10], mammary gland cells [11], neurons [12] and other types.…”

Coordination of actin plus-end dynamics by IQGAP1, formin, and capping protein

“…IQ-motif containing GTPase activating protein 1 (IQGAP1) is a conserved 189 kDa scaffolding protein that coordinates actin and microtubule dynamics, cell signaling pathways, and other essential cell processes [27][28][29][30][31][32][33] . IQGAP1 influences actin filaments in two ways: filament bundling via an Nterminal calponin homology domain (CHD), and transient suppression of plus end growth via residues located in its C-terminus (744-1657) [34][35][36][37][38] .…”