PI3Kβ-A Versatile Transducer for GPCR, RTK, and Small GTPase Signaling

Research output: Contribution to journalArticle

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Abstract

The phosphoinositide 3-kinase (PI3K) family includes eight distinct catalytic subunits and seven regulatory subunits. Only two PI3Ks are directly regulated downstream from G protein-coupled receptors (GPCRs): the class I enzymes PI3Kβ and PI3Kγ. Both enzymes produce phosphatidylinositol 3,4,5-trisposphate in vivo and are regulated by both heterotrimeric G proteins and small GTPases from the Ras or Rho families. However, PI3Kβ is also regulated by direct interactions with receptor tyrosine kinases (RTKs) and their tyrosine phosphorylated substrates, and similar to the class II and III PI3Ks, it binds activated Rab5. The unusually complex regulation of PI3Kβ by small and trimeric G proteins and RTKs leads to a rich landscape of signaling responses at the cellular and organismic levels. This review focuses first on the regulation of PI3Kβ activity in vitro and in cells, and then summarizes the biology of PI3Kβ signaling in distinct tissues and in human disease.

Original languageEnglish (US)
Pages (from-to)536-555
Number of pages20
JournalEndocrinology
Volume160
Issue number3
DOIs
StatePublished - Mar 1 2019

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1-Phosphatidylinositol 4-Kinase
Monomeric GTP-Binding Proteins
Receptor Protein-Tyrosine Kinases
G-Protein-Coupled Receptors
Transducers
Phosphatidylinositol 3-Kinases
Heterotrimeric GTP-Binding Proteins
Enzymes
Phosphatidylinositols
Protein-Tyrosine Kinases
Tyrosine
Catalytic Domain

ASJC Scopus subject areas

  • Endocrinology

Cite this

PI3Kβ-A Versatile Transducer for GPCR, RTK, and Small GTPase Signaling. / Bresnick, Anne R.; Backer, Jonathan M.

In: Endocrinology, Vol. 160, No. 3, 01.03.2019, p. 536-555.

Research output: Contribution to journalArticle

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