Structural comparisons of class i phosphoinositide 3-kinases

ABSTRACT Class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that regulate cell growth. One of these kinases, PI3Kα, is frequently mutated in diverse tumour types. The recently

determined structure of PI3Kα reveals features that distinguish this enzyme from related lipid kinases. In addition, wild-type PI3Kγ differs from PI3Kα by a substitution identical to a PI3Kα

oncogenic mutant (His1047Arg) that might explain the differences in the enzymatic activities of the normal and mutant PI3Kα. Comparison of the PI3K structures also identified structural

features that could potentially be exploited for the design of isoform-specific inhibitors. Access through your institution Buy or subscribe This is a preview of subscription content, access

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MECHANISMS TO THERAPEUTIC OPPORTUNITIES Article 03 April 2025 STRUCTURAL BASIS OF PHOSPHATIDYLINOSITOL 3-KINASE C2Α FUNCTION Article Open access 07 March 2022 BEYOND PI3KS: TARGETING

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ACKNOWLEDGEMENTS Support was provided by the Virginia and D. K. Ludwig Fund for Cancer Research, NIH grants CA43460 to B.V., GM066895 to L.M.A, and GM07309 and GM07184 to D.M. AUTHOR

INFORMATION Author notes * L. Mario Amzel and Chuan-Hsiang Huang: L.M.A and C.-H.H. contributed equally to this work. AUTHORS AND AFFILIATIONS * Chuan-Hsiang Huang and Sandra B. Gabelli are

at the Department of Biophysics and Biophysical Chemistry,Johns Hopkins University School of Medicine, L. Mario Amzel, 725 North Wolfe Street, Baltimore, Maryland 21205, USA., L. Mario

Amzel, Chuan-Hsiang Huang & Sandra B. Gabelli * Chuan-Hsiang Huang is at the Graduate Program in Immunology, Johns Hopkins University School of Medicine, 725 North Wolfe Street,

Baltimore, Maryland 21205, USA., Chuan-Hsiang Huang * Diana Mandelker, Christoph Lengauer and Bert Vogelstein are at the Ludwig Center for Cancer Genetics and Therapeutics, and The Howard

Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, 1,650 Orleans Street, Baltimore, Maryland 21231, USA., Diana Mandelker, Christoph Lengauer & Bert Vogelstein *

Christoph Lengauer is currently at the Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA Christoph Lengauer Authors * L. Mario Amzel

View author publications You can also search for this author inPubMed Google Scholar * Chuan-Hsiang Huang View author publications You can also search for this author inPubMed Google

Scholar * Diana Mandelker View author publications You can also search for this author inPubMed Google Scholar * Christoph Lengauer View author publications You can also search for this

author inPubMed Google Scholar * Sandra B. Gabelli View author publications You can also search for this author inPubMed Google Scholar * Bert Vogelstein View author publications You can

also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Bert Vogelstein. ETHICS DECLARATIONS COMPETING INTERESTS Under agreements between the Johns Hopkins

Universtiy and Exact Sciences, Inc., B. V. is entitled to a share of the royalties received by the University on sales of products related to PIK3CA mutations. The University and B. V. also

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and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Amzel, L., Huang, CH., Mandelker, D. _et al._ Structural comparisons of class I phosphoinositide 3-kinases. _Nat Rev Cancer_ 8, 665–669

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