Dorsal Ruffles Enhance Activation of Akt by Growth Factors

Abstract

SummaryIn fibroblasts, platelet-derived growth factor (PDGF) stimulates macropinocytosis and PI 3-kinase (PI3K)-dependent phosphorylation of Akt, leading to activation of mTORC1, a protein complex controlling metabolism and cell growth. PIP3, the phosphoinositide product of PI3K that activates Akt, is frequently concentrated within the macropinocytic cups of growth factorstimulated cells, which suggests that cup structure enhances phosphorylation of Akt by facilitating PI3K activity. However, inhibitors of the cytoskeleton which block cup formation do Stimulation with low concentrations of PDGF elicited lower levels of Akt phosphorylation, which, like responses to EGF, were inhibited by nocodazole. These results indicate that when receptor signaling generates low levels of PI3K activity, CDR facilitate local amplification of PI3K, PIP3 synthesis and phosphorylation of Akt.All rights reserved. No reuse allowed without permission.

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

“…The present work suggests that activating mutations of Akt, and possibly SGK, could drive macropinocytic feeding in mammalian cells, increasing the size of macropinosomes and hence nutrient acquisition. Consistent with this hypothesis, recent studies have shown Akt to be activated at sites of macropinocytosis, while inhibition of macropinocytosis inhibits Akt activation (Chiasson-MacKenzie et al, 2018; Erami et al, 2017; Yoshida et al, 2018). Akt inhibition does not depress macropinosome formation in macrophages, although these studies did not rule out smaller macropinosomes and reduced fluid uptake (Pacitto et al, 2017; Yoshida et al, 2015).…”

Stimulating Macropinocytosis for Intracellular Nucleic Acid and Protein Delivery: A Combined Strategy with Membrane-Lytic Peptides To Facilitate Endosomal Escape

“…Dynamic actin reorganization, seen as veil-like actin accumulation and protrusions at the cell periphery (i.e., lamellipodia), accompanies macropinocytosis. 28 Observing the formation of the said structure should further indicate the ability of SN21 to activate macropinocytosis. We performed time-lapse confocal laser scanning microscopy (CLSM) on HeLa cells expressing Lifeact-mCherry [visualizing filamentous actin (F-actin) structures] treated with SN21.…”

Akt kinases are required for efficient feeding by macropinocytosis inDictyostelium

“…PIP3 is required for effective macropinocytosis in mammalian cells, but the role of Akt is less clear (Araki et al, 1996). Inducing macropinosome formation activates Akt at macropinosomes, and this activation can be inhibited with macropinocytosis inhibitors (Chiasson-MacKenzie et al, 2018; Erami et al, 2017; Yoshida et al, 2018 preprint). However, macropinosome formation is not affected by inhibition of Akt in macrophages (Pacitto et al, 2017; Yoshida et al, 2015).…”