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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Segerer, G; Engelmann, D; Kaestner, A; Trötzmüller, M; Köfeler, H; Stigloher, C; Thiele, C; Jeanclos, E; Gohla, A.
A phosphoglycolate phosphatase/AUM-dependent link between triacylglycerol turnover and epidermal growth factor signaling.
Biochim Biophys Acta. 2018; 1863(6):584-594
Doi: 10.1016/j.bbalip.2018.03.002
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Köfeler Harald
- Trötzmüller Martin
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- Abstract:
- Mammalian phosphoglycolate phosphatase (PGP, also known as AUM or glycerol-3-phosphate phosphatase) is a small molecule-directed phosphatase important for metabolite repair and lipid metabolism. Although PGP was first characterized as an enzyme involved in epidermal growth factor (EGF) signaling, PGP protein substrates have remained elusive. Here we show that PGP depletion facilitates fatty acid flux through the intracellular triacylglycerol/fatty acid cycle, and that phosphatidylinositol-4,5-bisphosphate (PIP2), produced in a side branch of this cycle, is critical for the impact of PGP activity on EGF-induced signaling. Loss of endogenous PGP expression amplified both EGF-induced EGF receptor autophosphorylation and Src-dependent tyrosine phosphorylation of phospholipase C-γ1 (PLCγ1). Furthermore, EGF enhanced the formation of circular dorsal ruffles in PGP-depleted cells via Src/PLCγ1/protein kinase C (PKC)-dependent signaling to the cytoskeleton. Inhibition of adipose triglyceride lipase normalized the increased PIP2 content, reduced EGF-dependent PLCγ1 hyperphosphorylation, and decreased the elevated dorsal ruffle formation of PGP-depleted cells. Our data explain how PGP exerts control over EGF-induced cellular protein tyrosine phosphorylation, and reveal an unexpected influence of triacylglycerol turnover on growth factor signaling. Copyright © 2018 Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Line -
- Epidermal Growth Factor - genetics
- Epidermal Growth Factor - metabolism
- Humans -
- Phosphatidylinositol 4,5-Diphosphate - genetics
- Phosphatidylinositol 4,5-Diphosphate - metabolism
- Phospholipase C gamma - genetics
- Phospholipase C gamma - metabolism
- Phosphoric Monoester Hydrolases - genetics
- Phosphoric Monoester Hydrolases - metabolism
- Protein Kinase C - genetics
- Protein Kinase C - metabolism
- Signal Transduction -
- Triglycerides - genetics
- Triglycerides - metabolism
- Find related publications in this database (Keywords)
- AUM
- Circular dorsal ruffle
- Epidermal growth factor receptor
- Glycerol-3-phosphate phosphatase
- Phosphoglycolate phosphatase
- Triacylglycerol/fatty acid cycle