PI3Kβ is selectively required for growth factor-stimulated macropinocytosis

Gilbert Salloum, Charles T. Jakubik, Zahra Erami, Samantha D. Heitz, Anne R. Bresnick, Jonathan M. Backer

Research output: Contribution to journalArticle

Abstract

Macropinocytosis is an actin-dependent but clathrin-independent endocytic process by which cells nonselectively take up large aliquots of extracellular material. Macropinocytosis is used for immune surveillance by dendritic cells, as a route of infection by viruses and protozoa, and as a nutrient uptake pathway in tumor cells. In this study, we explore the role of class I phosphoinositide 3-kinases (PI3Ks) during ligand-stimulated macropinocytosis. We find that macropinocytosis in response to receptor tyrosine kinase activation is strikingly dependent on a single class I PI3K isoform, namely PI3Kβ (containing the p110β catalytic subunit encoded by PIK3CB). Loss of PI3Kβ expression or activity blocks macropinocytosis at early steps, before the formation of circular dorsal ruffles, but also plays a role in later steps, downstream from Rac1 activation. PI3Kβ is also required for the elevated levels of constitutive macropinocytosis found in tumor cells that are defective for the PTEN tumor suppressor. Our data shed new light on PI3K signaling during macropinocytosis, and suggest new therapeutic uses for pharmacological inhibitors of PI3Kβ.

Original languageEnglish (US)
JournalJournal of cell science
Volume132
Issue number16
DOIs
StatePublished - Aug 16 2019

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1-Phosphatidylinositol 4-Kinase
Intercellular Signaling Peptides and Proteins
Neoplasms
Clathrin
Receptor Protein-Tyrosine Kinases
Therapeutic Uses
Virus Diseases
Dendritic Cells
Actins
Catalytic Domain
Protein Isoforms
Pharmacology
Ligands

Keywords

  • Circular dorsal ruffles
  • HGF
  • Macropinocytosis
  • PDGF
  • Phosphoinositide 3-kinase
  • PIK3CB
  • PTEN
  • Rac
  • Tumor cells

ASJC Scopus subject areas

  • Cell Biology

Cite this

PI3Kβ is selectively required for growth factor-stimulated macropinocytosis. / Salloum, Gilbert; Jakubik, Charles T.; Erami, Zahra; Heitz, Samantha D.; Bresnick, Anne R.; Backer, Jonathan M.

In: Journal of cell science, Vol. 132, No. 16, 16.08.2019.

Research output: Contribution to journalArticle

Salloum, Gilbert ; Jakubik, Charles T. ; Erami, Zahra ; Heitz, Samantha D. ; Bresnick, Anne R. ; Backer, Jonathan M. / PI3Kβ is selectively required for growth factor-stimulated macropinocytosis. In: Journal of cell science. 2019 ; Vol. 132, No. 16.
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