Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling

Choi, Eunhee; Kikuchi, Sotaro; Gao, Haishan; Brodzik, Karolina; Nassour, Ibrahim; Yopp, Adam; Singal, Amit G.; Zhu, Hao; Yu, Hongtao

doi:10.1038/s41467-019-09318-3

Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling

Journal Article · Mon Apr 01 00:00:00 UTC 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-09318-3· OSTI ID:1566812

Choi, Eunhee ^[1]; Kikuchi, Sotaro ^[1]; Gao, Haishan ^[1]; Brodzik, Karolina ^[1]; Nassour, Ibrahim ^[1]; Yopp, Adam ^[1]; Singal, Amit G. ^[1]; ^[1]; ^[1]

Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

Insulin controls glucose homeostasis and cell growth through bifurcated signaling pathways. Dysregulation of insulin signaling is linked to diabetes and cancer. The spindle checkpoint controls the fidelity of chromosome segregation during mitosis. Here, we show that insulin receptor substrate 1 and 2 (IRS1/2) cooperate with spindle checkpoint proteins to promote insulin receptor (IR) endocytosis through recruiting the clathrin adaptor complex AP2 to IR. A phosphorylation switch of IRS1/2 orchestrated by extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Src homology phosphatase 2 (SHP2) ensures selective internalization of activated IR. SHP2 inhibition blocks this feedback regulation and growth-promoting IR signaling, prolongs insulin action on metabolism, and improves insulin sensitivity in mice. We propose that mitotic regulators and SHP2 promote feedback inhibition of IR, thereby limiting the duration of insulin signaling. Targeting this feedback inhibition can improve insulin sensitivity.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

OSTI ID:: 1566812

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (94)

Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2 Copps, K. D.; White, M. F. Diabetologia, Vol. 55, Issue 10 https://doi.org/10.1007/s00125-012-2644-8	journal	August 2012
Liver-specific reconstitution of CEACAM1 reverses the metabolic abnormalities caused by its global deletion in male mice Russo, Lucia; Muturi, Harrison T.; Ghadieh, Hilda E. Diabetologia, Vol. 60, Issue 12 https://doi.org/10.1007/s00125-017-4432-y	journal	September 2017
p31comet Blocks Mad2 Activation through Structural Mimicry Yang, Maojun; Li, Bing; Tomchick, Diana R. Cell, Vol. 131, Issue 4 https://doi.org/10.1016/j.cell.2007.08.048	journal	November 2007
Mitotic Checkpoint Regulators Control Insulin Signaling and Metabolic Homeostasis Choi, Eunhee; Zhang, Xiangli; Xing, Chao Cell, Vol. 166, Issue 3 https://doi.org/10.1016/j.cell.2016.05.074	journal	July 2016
Selective versus Total Insulin Resistance: A Pathogenic Paradox Brown, Michael S.; Goldstein, Joseph L. Cell Metabolism, Vol. 7, Issue 2 https://doi.org/10.1016/j.cmet.2007.12.009	journal	February 2008
The role of Shp2 (PTPN11) in cancer Mohi, M. Golam; Neel, Benjamin G. Current Opinion in Genetics & Development, Vol. 17, Issue 1 https://doi.org/10.1016/j.gde.2006.12.011	journal	February 2007
Protein Metamorphosis: The Two-State Behavior of Mad2 Luo, Xuelian; Yu, Hongtao Structure, Vol. 16, Issue 11 https://doi.org/10.1016/j.str.2008.10.002	journal	November 2008
Tracking spindle checkpoint signals from kinetochores to APC/C Jia, Luying; Kim, Soonjoung; Yu, Hongtao Trends in Biochemical Sciences, Vol. 38, Issue 6 https://doi.org/10.1016/j.tibs.2013.03.004	journal	June 2013
Sequencing analysis of insulin receptor defects and detection of two novel mutations in INSR gene Ardon, O.; Procter, M.; Tvrdik, T. Molecular Genetics and Metabolism Reports, Vol. 1 https://doi.org/10.1016/j.ymgmr.2013.12.006	journal	January 2014
The β2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase BubR1 Cayrol, Corinne; Cougoule, Céline; Wright, Michel Biochemical and Biophysical Research Communications, Vol. 298, Issue 5 https://doi.org/10.1016/s0006-291x(02)02522-6	journal	November 2002
Structure of the IRS-1 PTB Domain Bound to the Juxtamembrane Region of the Insulin Receptor Eck, Michael J.; Dhe-Paganon, Sirano; Trüb, Thomas Cell, Vol. 85, Issue 5 https://doi.org/10.1016/s0092-8674(00)81236-2	journal	May 1996
Direct Binding of CDC20 Protein Family Members Activates the Anaphase-Promoting Complex in Mitosis and G1 Fang, Guowei; Yu, Hongtao; Kirschner, Marc W. Molecular Cell, Vol. 2, Issue 2 https://doi.org/10.1016/s1097-2765(00)80126-4	journal	August 1998
The Mad2 Spindle Checkpoint Protein Undergoes Similar Major Conformational Changes Upon Binding to Either Mad1 or Cdc20 Luo, Xuelian; Tang, Zhanyun; Rizo, Josep Molecular Cell, Vol. 9, Issue 1 https://doi.org/10.1016/s1097-2765(01)00435-x	journal	January 2002
Tracing the Pathway of Spindle Assembly Checkpoint Signaling Gillett, Emily S.; Sorger, Peter K. Developmental Cell, Vol. 1, Issue 2 https://doi.org/10.1016/s1534-5807(01)00032-6	journal	August 2001
High-Precision Isothermal Titration Calorimetry with Automated Peak-Shape Analysis Keller, Sandro; Vargas, Carolyn; Zhao, Huaying Analytical Chemistry, Vol. 84, Issue 11 https://doi.org/10.1021/ac3007522	journal	June 2012
Crystal structure of the tyrosine kinase domain of the human insulin receptor Hubbard, Stevan R.; Wei, Lei; Hendrickson, Wayne A. Nature, Vol. 372, Issue 6508 https://doi.org/10.1038/372746a0	journal	December 1994
Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases Chen, Ying-Nan P.; LaMarche, Matthew J.; Chan, Ho Man Nature, Vol. 535, Issue 7610 https://doi.org/10.1038/nature18621	journal	June 2016
BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice Baker, Darren J.; Jeganathan, Karthik B.; Cameron, J. Douglas Nature Genetics, Vol. 36, Issue 7 https://doi.org/10.1038/ng1382	journal	June 2004
Critical nodes in signalling pathways: insights into insulin action Taniguchi, Cullen M.; Emanuelli, Brice; Kahn, C. Ronald Nature Reviews Molecular Cell Biology, Vol. 7, Issue 2 https://doi.org/10.1038/nrm1837	journal	February 2006
Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle checkpoint silencing Brulotte, Melissa L.; Jeong, Byung-Cheon; Li, Faxiang Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-02012-2	journal	December 2017
Conformation-specific binding of p31comet antagonizes the function of Mad2 in the spindle checkpoint Xia, Guohong; Luo, Xuelian; Habu, Toshiyuki The EMBO Journal, Vol. 23, Issue 15 https://doi.org/10.1038/sj.emboj.7600322	journal	July 2004
Mechanism of feedback regulation of insulin receptor substrate-1 phosphorylation in primary adipocytes Hers, Ingeborg; TavarÉ, Jeremy M. Biochemical Journal, Vol. 388, Issue 2 https://doi.org/10.1042/bj20041531	journal	May 2005
Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism Zhang, E. E.; Chapeau, E.; Hagihara, K. Proceedings of the National Academy of Sciences, Vol. 101, Issue 45 https://doi.org/10.1073/pnas.0405041101	journal	November 2004
Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic -cells Zhang, S. S.; Hao, E.; Yu, J. Proceedings of the National Academy of Sciences, Vol. 106, Issue 18 https://doi.org/10.1073/pnas.0811715106	journal	April 2009
Structure of human Mad1 C-terminal domain reveals its involvement in kinetochore targeting Kim, S.; Sun, H.; Tomchick, D. R. Proceedings of the National Academy of Sciences, Vol. 109, Issue 17 https://doi.org/10.1073/pnas.1118210109	journal	April 2012
PTB Domains of IRS-1 and Shc Have Distinct but Overlapping Binding Specificities Wolf, Gert; Trüb, Thomas; Ottinger, Elizabeth Journal of Biological Chemistry, Vol. 270, Issue 46 https://doi.org/10.1074/jbc.270.46.27407	journal	November 1995
Interaction of Insulin Receptor Substrate-2 (IRS-2) with the Insulin and Insulin-like Growth Factor I Receptors: EVIDENCE FOR TWO DISTINCT PHOSPHOTYROSINE-DEPENDENT INTERACTION DOMAINS WITHIN IRS-2 He, Weimin; Craparo, Ann; Zhu, Youyan Journal of Biological Chemistry, Vol. 271, Issue 20 https://doi.org/10.1074/jbc.271.20.11641	journal	May 1996
Dual Role of a Dileucine Motif in Insulin Receptor Endocytosis Hamer, Isabelle; Haft, Carol Renfrew; Paccaud, Jean-Pierre Journal of Biological Chemistry, Vol. 272, Issue 35 https://doi.org/10.1074/jbc.272.35.21685	journal	August 1997
Modulation of Insulin Receptor Substrate-1 Tyrosine Phosphorylation and Function by Mitogen-activated Protein Kinase De Fea, Kathryn; Roth, Richard A. Journal of Biological Chemistry, Vol. 272, Issue 50 https://doi.org/10.1074/jbc.272.50.31400	journal	December 1997
The COOH-terminal Tyrosine Phosphorylation Sites on IRS-1 Bind SHP-2 and Negatively Regulate Insulin Signaling Myers, Martin G.; Mendez, Raul; Shi, Ping Journal of Biological Chemistry, Vol. 273, Issue 41 https://doi.org/10.1074/jbc.273.41.26908	journal	October 1998
Altered Glucose Homeostasis in Mice with Liver-specific Deletion of Src Homology Phosphatase 2 Matsuo, Kosuke; Delibegovic, Mirela; Matsuo, Izumi Journal of Biological Chemistry, Vol. 285, Issue 51 https://doi.org/10.1074/jbc.m110.153734	journal	September 2010
The Cdc20-binding Phe Box of the Spindle Checkpoint Protein BubR1 Maintains the Mitotic Checkpoint Complex During Mitosis Diaz-Martinez, Laura A.; Tian, Wei; Li, Bing Journal of Biological Chemistry, Vol. 290, Issue 4 https://doi.org/10.1074/jbc.m114.616490	journal	December 2014
Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 Sudakin, Valery; Chan, Gordon K. T.; Yen, Tim J. The Journal of Cell Biology, Vol. 154, Issue 5 https://doi.org/10.1083/jcb.200102093	journal	September 2001
Regulation of reproduction and longevity by nutrient-sensing pathways Templeman, Nicole M.; Murphy, Coleen T. The Journal of Cell Biology, Vol. 217, Issue 1 https://doi.org/10.1083/jcb.201707168	journal	October 2017
Insulin Receptor Signaling in Normal and Insulin-Resistant States Boucher, J.; Kleinridders, A.; Kahn, C. R. Cold Spring Harbor Perspectives in Biology, Vol. 6, Issue 1 https://doi.org/10.1101/cshperspect.a009191	journal	January 2014
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes Minor, Wladek; Cymborowski, Marcin; Otwinowski, Zbyszek Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8 https://doi.org/10.1107/s0907444906019949	journal	July 2006
Solving structures of protein complexes by molecular replacement with Phaser McCoy, Airlie J. Acta Crystallographica Section D Biological Crystallography, Vol. 63, Issue 1 https://doi.org/10.1107/s0907444906045975	journal	December 2006
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/s0907444909042073	journal	December 2009
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/s0907444910007493	journal	March 2010
Insulin Signaling in Health and Disease White, M. F. Science, Vol. 302, Issue 5651 https://doi.org/10.1126/science.1092952	journal	December 2003
Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death Princen, F.; Bard, E.; Sheikh, F. Molecular and Cellular Biology, Vol. 29, Issue 2 https://doi.org/10.1128/mcb.01661-08	journal	November 2008
YMXM motifs and signaling by an insulin receptor substrate 1 molecule without tyrosine phosphorylation sites. Myers, M. G.; Zhang, Y.; Aldaz, G. A. Molecular and Cellular Biology, Vol. 16, Issue 8 https://doi.org/10.1128/mcb.16.8.4147	journal	August 1996
Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity. Caro, J. F.; Ittoop, O.; Pories, W. J. Journal of Clinical Investigation, Vol. 78, Issue 1 https://doi.org/10.1172/jci112558	journal	July 1986
Hepatic Src Homology Phosphatase 2 Regulates Energy Balance in Mice Nagata, Naoto; Matsuo, Kosuke; Bettaieb, Ahmed Endocrinology, Vol. 153, Issue 7 https://doi.org/10.1210/en.2012-1406	journal	July 2012
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
SHP2 phosphatase as a novel therapeutic target for melanoma treatment Zhang, Ruo-Yu; Yu, Zhi-Hong; Zeng, Lifan Oncotarget, Vol. 7, Issue 45 https://doi.org/10.18632/oncotarget.12074	journal	September 2016
Banting Lecture 2011: Hyperinsulinemia: Cause or Consequence? Corkey, B. E. Diabetes, Vol. 61, Issue 1 https://doi.org/10.2337/db11-1483	journal	December 2011
Micromanaging checkpoint proteins Ciliberto, Andrea; Hauf, Silke eLife, Vol. 6 https://doi.org/10.7554/elife.25001	journal	February 2017
Basal state hyperinsulinemia in healthy normoglycemic adults heralds dysglycemia after more than two decades of follow up: Hyperinsulinemia Heralds Dysglycemia Dankner, R.; Chetrit, A.; Shanik, M. H. Diabetes/Metabolism Research and Reviews, Vol. 28, Issue 7 https://doi.org/10.1002/dmrr.2322	journal	October 2012
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
The β2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase BubR1 Cayrol, Corinne; Cougoule, Céline; Wright, Michel Biochemical and Biophysical Research Communications, Vol. 298, Issue 5 https://doi.org/10.1016/S0006-291X(02)02522-6	journal	November 2002
Receptor-mediated internalization of insulin requires a 12-amino acid sequence in the juxtamembrane region of the insulin receptor beta-subunit. Backer, J. M.; Kahn, C. R.; Cahill, D. A. Journal of Biological Chemistry, Vol. 265, Issue 27 https://doi.org/10.1016/S0021-9258(17)46243-0	journal	September 1990
Involvement of dileucine motifs in the internalization and degradation of the insulin receptor Haft, C. R.; Klausner, R. D.; Taylor, S. I. Journal of Biological Chemistry, Vol. 269, Issue 42 https://doi.org/10.1016/S0021-9258(18)47192-X	journal	October 1994
Insulin binding to liver plasm membranes in the obese hyperglycemic (ob/ob) mouse. Demonstration of a decreased number of functionally normal receptors. Soll, A. H.; Kahn, C. R.; Neville, D. M. Journal of Biological Chemistry, Vol. 250, Issue 12 https://doi.org/10.1016/S0021-9258(19)41358-6	journal	June 1975
Crystal Structure of the Tyrosine Phosphatase SHP-2 Hof, Peter; Pluskey, Scott; Dhe-Paganon, Sirano Cell, Vol. 92, Issue 4 https://doi.org/10.1016/S0092-8674(00)80938-1	journal	February 1998
Structure of the IRS-1 PTB Domain Bound to the Juxtamembrane Region of the Insulin Receptor Eck, Michael J.; Dhe-Paganon, Sirano; Trüb, Thomas Cell, Vol. 85, Issue 5 https://doi.org/10.1016/S0092-8674(00)81236-2	journal	May 1996
Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity White, Morris F.; Livingston, James N.; Backer, Jonathan M. Cell, Vol. 54, Issue 5 https://doi.org/10.1016/S0092-8674(88)80008-4	journal	August 1988
Direct Binding of CDC20 Protein Family Members Activates the Anaphase-Promoting Complex in Mitosis and G1 Fang, Guowei; Yu, Hongtao; Kirschner, Marc W. Molecular Cell, Vol. 2, Issue 2 https://doi.org/10.1016/S1097-2765(00)80126-4	journal	August 1998
The Mad2 Spindle Checkpoint Protein Undergoes Similar Major Conformational Changes Upon Binding to Either Mad1 or Cdc20 Luo, Xuelian; Tang, Zhanyun; Rizo, Josep Molecular Cell, Vol. 9, Issue 1 https://doi.org/10.1016/S1097-2765(01)00435-X	journal	January 2002
Loss of Insulin Signaling in Hepatocytes Leads to Severe Insulin Resistance and Progressive Hepatic Dysfunction Michael, M. Dodson; Kulkarni, Rohit N.; Postic, Catherine Molecular Cell, Vol. 6, Issue 1 https://doi.org/10.1016/S1097-2765(05)00015-8	journal	July 2000
Mad2-Independent Inhibition of APCCdc20 by the Mitotic Checkpoint Protein BubR1 Tang, Zhanyun; Bharadwaj, Rajnish; Li, Bing Developmental Cell, Vol. 1, Issue 2 https://doi.org/10.1016/S1534-5807(01)00019-3	journal	August 2001
Sticking It to Cancer with Molecular Glue for SHP2 Ran, Hao; Tsutsumi, Ryouhei; Araki, Toshiyuki Cancer Cell, Vol. 30, Issue 2 https://doi.org/10.1016/j.ccell.2016.07.010	journal	August 2016
Mechanisms for Insulin Resistance: Common Threads and Missing Links Samuel, Varman T.; Shulman, Gerald I. Cell, Vol. 148, Issue 5 https://doi.org/10.1016/j.cell.2012.02.017	journal	March 2012
The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics Musacchio, Andrea Current Biology, Vol. 25, Issue 20 https://doi.org/10.1016/j.cub.2015.08.051	journal	October 2015
The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics Musacchio, Andrea Current Biology, Vol. 25, Issue 22 https://doi.org/10.1016/j.cub.2015.10.050	journal	November 2015
Structure of the mitotic checkpoint complex Chao, William C. H.; Kulkarni, Kiran; Zhang, Ziguo Nature, Vol. 484, Issue 7393 https://doi.org/10.1038/nature10896	journal	March 2012
Molecular basis of APC/C regulation by the spindle assembly checkpoint Alfieri, Claudio; Chang, Leifu; Zhang, Ziguo Nature, Vol. 536, Issue 7617 https://doi.org/10.1038/nature19083	journal	August 2016
Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing? Klil-Drori, Adi J.; Azoulay, Laurent; Pollak, Michael N. Nature Reviews Clinical Oncology, Vol. 14, Issue 2 https://doi.org/10.1038/nrclinonc.2016.120	journal	August 2016
Tickets to ride: selecting cargo for clathrin-regulated internalization Traub, Linton M. Nature Reviews Molecular Cell Biology, Vol. 10, Issue 9 https://doi.org/10.1038/nrm2751	journal	September 2009
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
The oligomeric structures of plant cryptochromes Shao, Kai; Zhang, Xue; Li, Xu Nature Structural & Molecular Biology, Vol. 27, Issue 5 https://doi.org/10.1038/s41594-020-0420-x	journal	May 2020
Mechanism of feedback regulation of insulin receptor substrate-1 phosphorylation in primary adipocytes Hers, Ingeborg; TavarÉ, Jeremy M. Biochemical Journal, Vol. 388, Issue 2 https://doi.org/10.1042/BJ20041531	journal	May 2005
Altered Glucose Homeostasis in Mice with Liver-specific Deletion of Src Homology Phosphatase 2 Matsuo, Kosuke; Delibegovic, Mirela; Matsuo, Izumi Journal of Biological Chemistry, Vol. 285, Issue 51 https://doi.org/10.1074/jbc.M110.153734	journal	September 2010
The Cdc20-binding Phe Box of the Spindle Checkpoint Protein BubR1 Maintains the Mitotic Checkpoint Complex During Mitosis Diaz-Martinez, Laura A.; Tian, Wei; Li, Bing Journal of Biological Chemistry, Vol. 290, Issue 4 https://doi.org/10.1074/jbc.M114.616490	journal	December 2014
Insulin receptors internalize by a rapid, saturable pathway requiring receptor autophosphorylation and an intact juxtamembrane region Backer, J. M. The Journal of Cell Biology, Vol. 115, Issue 6 https://doi.org/10.1083/jcb.115.6.1535	journal	December 1991
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes Minor, Wladek; Cymborowski, Marcin; Otwinowski, Zbyszek Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8 https://doi.org/10.1107/S0907444906019949	journal	July 2006
Solving structures of protein complexes by molecular replacement with Phaser McCoy, Airlie J. Acta Crystallographica Section D Biological Crystallography, Vol. 63, Issue 1 https://doi.org/10.1107/S0907444906045975	journal	December 2006
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death Princen, F.; Bard, E.; Sheikh, F. Molecular and Cellular Biology, Vol. 29, Issue 2 https://doi.org/10.1128/MCB.01661-08	journal	November 2008
Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1. Sun, X. J.; Crimmins, D. L.; Myers, M. G. Molecular and Cellular Biology, Vol. 13, Issue 12 https://doi.org/10.1128/MCB.13.12.7418	journal	December 1993
Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Gustafson, T. A.; He, W.; Craparo, A. Molecular and Cellular Biology, Vol. 15, Issue 5 https://doi.org/10.1128/MCB.15.5.2500	journal	May 1995
YMXM motifs and signaling by an insulin receptor substrate 1 molecule without tyrosine phosphorylation sites. Myers, M. G.; Zhang, Y.; Aldaz, G. A. Molecular and Cellular Biology, Vol. 16, Issue 8 https://doi.org/10.1128/MCB.16.8.4147	journal	August 1996
Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1 Sun, X. J.; Crimmins, D. L.; Myers, M. G. Molecular and Cellular Biology, Vol. 13, Issue 12 https://doi.org/10.1128/mcb.13.12.7418-7428.1993	journal	December 1993
Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity. Caro, J. F.; Ittoop, O.; Pories, W. J. Journal of Clinical Investigation, Vol. 78, Issue 1 https://doi.org/10.1172/JCI112558	journal	July 1986
Insulin signaling in health and disease Saltiel, Alan R. Journal of Clinical Investigation, Vol. 131, Issue 1 https://doi.org/10.1172/JCI142241	journal	January 2021
The Mad2 Spindle Checkpoint Protein Undergoes Similar Major Conformational Changes upon Binding to Either Mad1 or Cdc20 Luo, X.; Tang, Z.; Rizo, J. Biological Magnetic Resonance Bank https://doi.org/10.13018/bmr5299	dataset	January 2002
Spindle Checkpoint Regulators in Insulin Signaling Choi, Eunhee; Yu, Hongtao Frontiers in Cell and Developmental Biology, Vol. 6 https://doi.org/10.3389/fcell.2018.00161	journal	November 2018
TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching Ye, Qiaozhen; Rosenberg, Scott C.; Moeller, Arne eLife, Vol. 4 https://doi.org/10.7554/eLife.07367	journal	April 2015
A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling Ji, Zhejian; Gao, Haishan; Jia, Luying eLife, Vol. 6 https://doi.org/10.7554/eLife.22513	journal	January 2017
IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained IGF signaling Yoneyama, Yosuke; Lanzerstorfer, Peter; Niwa, Hideaki eLife, Vol. 7 https://doi.org/10.7554/eLife.32893	journal	April 2018

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