Akt and SGK protein kinases are required for efficient feeding by macropinocytosis

Thomas D. Williams, Sew-Yeu Peak-Chew, Peggy Paschke, Robert R. Kay

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
28 Downloads (Pure)

Abstract

Macropinocytosis is an actin-driven process of large-scale and non-specific fluid uptake used for feeding by some cancer cells and the macropinocytosis model organism Dictyostelium discoideum. In Dictyostelium, macropinocytic cups are organized by ‘macropinocytic patches’ in the plasma membrane. These contain activated Ras, Rac and phospholipid PIP3, and direct actin polymerization to their periphery. We show that a Dictyostelium Akt (PkbA) and an SGK (PkbR1) protein kinase act downstream of PIP3 and, together, are nearly essential for fluid uptake. This pathway enables the formation of larger macropinocytic patches and macropinosomes, thereby dramatically increasing fluid uptake. Through phosphoproteomics, we identify a RhoGAP, GacG, as a PkbA and PkbR1 target, and show that it is required for efficient macropinocytosis and expansion of macropinocytic patches. The function of Akt and SGK in cell feeding through control of macropinosome size has implications for cancer cell biology.
Original languageEnglish
Article numberjcs224998
Number of pages14
JournalJournal of Cell Science
Volume132
Issue number2
DOIs
Publication statusPublished - Jan 2019

Keywords

  • Macropinocytosis
  • Akt
  • SGK
  • Phosphoinositide 3-kinase
  • PI3K
  • Endocytosis
  • Dictyostelium

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