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IQGAP1 makes PI(3)K signalling as easy as PIP, PIP2, PIP3

Nature Cell Biology volume 18, pages 1263–1265 (2016)Cite this article

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Despite being one of the most studied signalling pathways, precisely how phospholipid synthesis is regulated in the phosphoinositide signalling cascade remains unclear. The scaffold protein IQGAP1 is now shown to orchestrate the assembly of a multi-enzyme complex that streamlines PtdIns(3,4,5)P3 synthesis to facilitate Akt activation in response to extracellular stimuli.

Biological systems have evolved multiple mechanisms to improve the efficiency of enzymatic reactions. Synthesis of macromolecules such as DNA, RNA and protein, for example, involves reactions that rely on processivity, the ability of a given enzyme to catalyse consecutive reactions without releasing the substrate. In signal transduction pathways, processive or quasi-processive post-translational modifications are common mechanisms for increasing the speed of the cell's response to a given signal. Such is the case for receptor tyrosine kinases, including the PDGF and EGF receptors, and non-receptor kinases, such as the Src family and MEK, which can autophosphorylate or phosphorylate their substrates multiple times1,2,3. In this issue of Nature Cell Biology, Choi et al.4 describe a mechanism by which the synthesis of a key signalling lipid, phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3 or PIP3), is streamlined by IQ-motif-containing GTPase-activating protein 1 (IQGAP1) in a processive manner.

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Figure 1: A diagram depicting two modalities of phosphoinositide signalling; a processive mode and a non-processive mode.

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Authors and Affiliations

  1. Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston, 02118, Massachusetts, USA

    Lucia E. Rameh

  2. Department of Ophthalmology, Schepens Eye Research Institute/Mass Eye and Ear, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Ashley M. Mackey

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  1. Lucia E. Rameh
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  2. Ashley M. Mackey
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Correspondence to Lucia E. Rameh.

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Rameh, L., Mackey, A. IQGAP1 makes PI(3)K signalling as easy as PIP, PIP2, PIP3. Nat Cell Biol 18, 1263–1265 (2016). https://doi.org/10.1038/ncb3440

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