The CNK1 scaffold binds cytohesins and promotes insulin pathway signaling.

Genes & Development
Junghwa LimDeborah K Morrison

Abstract

Protein scaffolds play an important role in signal transduction, regulating the localization of signaling components and mediating key protein interactions. Here, we report that the major binding partners of the Connector Enhancer of KSR 1 (CNK1) scaffold are members of the cytohesin family of Arf guanine nucleotide exchange factors, and that the CNK1/cytohesin interaction is critical for activation of the PI3K/AKT cascade downstream from insulin and insulin-like growth factor 1 (IGF-1) receptors. We identified a domain located in the C-terminal region of CNK1 that interacts constitutively with the coiled-coil domain of the cytohesins, and found that CNK1 facilitates the membrane recruitment of cytohesin-2 following insulin stimulation. Moreover, through protein depletion and rescue experiments, we found that the CNK1/cytohesin interaction promotes signaling from plasma membrane-bound Arf GTPases to the phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) to generate a PIP(2)-rich microenvironment that is critical for the membrane recruitment of insulin receptor substrate 1 (IRS1) and signal transmission to the PI3K/AKT cascade. These findings identify CNK1 as a new positive regulator of insulin signaling.

References

Apr 17, 1999·The Journal of Biological Chemistry·I YaoY Takai
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·M TherrienG M Rubin
Jan 9, 2001·The Journal of Biological Chemistry·I VainshteinR A Roth
Jul 11, 2001·The Journal of Biological Chemistry·J K KlarlundM P Czech
Dec 14, 2001·The Journal of Biological Chemistry·Anthony N AnselmoMichael A White
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Pingtao TangMassimo Gadina
Oct 23, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kazuhiro OhtakaraMasaki Inagaki
Jun 12, 2003·The Journal of Biological Chemistry·Rory MitchellMelanie S Johnson
Aug 16, 2003·The Journal of Biological Chemistry·Kanamarlapudi Venkateswarlu
Oct 1, 2003·The EMBO Journal·Mélanie DouziechMarc Therrien
Oct 24, 2003·Molecular Pharmacology·Derek N RobertsonRory Mitchell
Nov 5, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas M LaniganKun-Liang Guan
Jan 30, 2004·Molecular and Cellular Biology·Aron B JaffeAlan Hall
Mar 19, 2004·Current Biology : CB·Ron BumeisterMichael A White
Apr 13, 2004·The Journal of Biological Chemistry·Shahrooz RabizadehBrian Seed
Apr 23, 2005·The Journal of Biological Chemistry·Algirdas ZiogasGerald Radziwill
May 3, 2006·Cellular Signalling·Patrick GiguèreJean-Luc Parent
Dec 15, 2006·Nature·Markus HafnerMichael Famulok
Apr 6, 2007·Molecular Biology of the Cell·Lee Ann CohenJulie G Donaldson
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Thanashan RajakulendranFrank Sicheri
Mar 11, 2008·Trends in Cell Biology·Kenneth R Myers, James E Casanova
Apr 26, 2008·Endocrine Reviews·Stephanie T PageWilliam J Bremner

❮ Previous
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Citations

May 19, 2011·Nature Reviews. Molecular Cell Biology·Julie G Donaldson, Catherine L Jackson
May 21, 2013·FEBS Letters·Danièle Stalder, Bruno Antonny
Apr 18, 2012·Critical Reviews in Biochemistry and Molecular Biology·Rama SoundararajanDavid Pearce
Nov 17, 2011·Experimental Cell Research·Myriam A AttarLorraine C Santy
Nov 22, 2011·Molecular and Cellular Endocrinology·Rama SoundararajanTim Ziera
Mar 16, 2011·Traffic·Alexander F RowlandDavid E James
Apr 14, 2015·Nature Chemical Biology·Malia B PottsMichael A White
Oct 16, 2010·Cell·Anke BillMichael Famulok
Mar 29, 2011·Biochimica Et Biophysica Acta·Xinbo ZhangArun K Rishi
Feb 16, 2011·Biochimica Et Biophysica Acta·Rafael D Fritz, Gerald Radziwill
Oct 23, 2016·Biochimica Et Biophysica Acta. Molecular Cell Research·Adrian FischerGerald Radziwill
Mar 12, 2015·Anais Da Academia Brasileira De Ciências·Rafael O AlvimPaulo C J L Santos
Aug 19, 2017·Science Advances·Adrian FischerGerald Radziwill
Jan 14, 2017·The Journal of Biological Chemistry·Bhavna ChawlaDavid B Sacks
Sep 5, 2020·Science·Brandon J DeKosky
Dec 30, 2014·Molecular Biology of the Cell·Jiangshu LiuTony J C Harris
Apr 3, 2013·Oncology Reports·Kedong XuQingguang Liu
May 16, 2019·Molecular Biology of the Cell·Elizabeth SztulRichard A Kahn
Jul 12, 2013·Angewandte Chemie·Mohamed HusseinMichael Famulok
May 16, 2014·The Journal of Biological Chemistry·Hee Jun ChoIra O Daar
Aug 9, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Veronica VellaAntonino Belfiore
Mar 29, 2012·Journal of Cell Science·Seung Ja Oh, Lorraine C Santy
Apr 4, 2013·Journal of Cell Science·Ines HahnMichael Hoch
Aug 26, 2014·Journal of Cell Science·Catherine L Jackson, Samuel Bouvet
Feb 1, 2019·Annals of Dermatology·Yoon Jin LeeMoon Kyun Cho
Jun 24, 2021·American Journal of Physiology. Cell Physiology·Fan BaoTian-Rui Xu

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