Class I PI3K Biology

Tihitina Y Aytenfisu; Hannah M Campbell; Mayukh Chakrabarti; L Mario Amzel; Sandra B Gabelli

doi:10.1007/978-3-031-06566-8_1

Class I PI3K Biology

Curr Top Microbiol Immunol. 2022:436:3-49. doi: 10.1007/978-3-031-06566-8_1.

Authors

Tihitina Y Aytenfisu¹, Hannah M Campbell¹, Mayukh Chakrabarti¹, L Mario Amzel¹, Sandra B Gabelli^{2

3

4}

Affiliations

¹ Department of Biophysics and Biophysical Chemistry, The Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
² Department of Biophysics and Biophysical Chemistry, The Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. gabelli@jhmi.edu.
³ Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. gabelli@jhmi.edu.
⁴ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. gabelli@jhmi.edu.

PMID: 36243838
DOI: 10.1007/978-3-031-06566-8_1

Abstract

This chapter is an introduction to phosphoinositide 3-kinases (PI3K), with class I PI3Ks as the central focus. First, the various PI3K isoforms in class I are presented with emphasis on their overall structure, subunits, subunit constitutive domains, domain-domain interactions, and functional relevance. This structural analysis is followed by a comprehensive history of seminal investigations into PI3K activity. Next, we highlight the divergent roles of the isoforms: PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ. This section details signaling pathways in which these PI3K isoforms are involved, including the key upstream regulators of PI3K activity and some downstream cellular effects. Nodes of the PI3K pathway are also presented. Inhibitors of some isoforms are discussed to give an overview of the basis of some immunotherapies that are being used to target cell signaling. Finally, the chapter ends with a discussion of the dysregulation of PI3Ks in diseases including APDS, asthma, arthritis, and oncogenic mutations.

Keywords: APDS; Arthritis; Asthma; B-cell signaling; Chronic inflammation; Class I PI3Ks; Oncogenic mutation; PI3K; Phosphoinositide-3-kinase; RTK signaling; Ras signaling; T-cell signaling; p101; p110β; p110γ; p110δ; p84; pl10α.

MeSH terms

Biology
Phosphatidylinositol 3-Kinases* / genetics
Phosphatidylinositol 3-Kinases* / metabolism
Phosphatidylinositols / pharmacology
Protein Isoforms / genetics
Protein Isoforms / metabolism
Protein Isoforms / pharmacology
Signal Transduction* / physiology

Substances

Phosphatidylinositols
Protein Isoforms