Dorsal ruffles enhance activation of Akt by growth factors.

Abstract:

:In fibroblasts, platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) stimulate the formation of actin-rich, circular dorsal ruffles (CDRs) and phosphatidylinositol 3-kinase (PI3K)-dependent phosphorylation of Akt. To test the hypothesis that CDRs increase synthesis of phosphorylated Akt1 (pAkt), we analyzed the contributions of CDRs to Akt phosphorylation in response to PDGF and EGF. CDRs appeared within several minutes of growth factor addition, coincident with a peak of pAkt. Microtubule depolymerization with nocodazole blocked CDR formation and inhibited phosphorylation of Akt in response to EGF but not PDGF. Quantitative immunofluorescence showed increased concentrations of Akt, pAkt and phosphatidylinositol (3,4,5)-trisphosphate (PIP3), the phosphoinositide product of PI3K that activates Akt, concentrated in CDRs and ruffles. EGF stimulated lower maximal levels of pAkt than did PDGF, which suggests that Akt phosphorylation requires amplification in CDRs only when PI3K activities are low. Accordingly, 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, CDRs facilitate local amplification of PI3K and phosphorylation of Akt.This article has an associated First Person interview with the first author of the paper.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Yoshida S,Pacitto R,Sesi C,Kotula L,Swanson JA

doi

10.1242/jcs.220517

subject

Has Abstract

pub_date

2018-11-16 00:00:00

issue

22

eissn

0021-9533

issn

1477-9137

pii

jcs.220517

journal_volume

131

pub_type

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