Epidermal growth factor receptor is activated by hyposmolarity and is an early signal modulating osmolyte efflux pathways in Swiss 3T3 fibroblasts

Rodrigo Franco, Ruth Lezama, Benito Ordaz, Herminia Pasantes-Morales

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Exposure of cultured Swiss 3T3 fibroblasts to 35% hyposmotic solution activated epidermal growth factor receptor (EGFR) phosphorylation to a greater extent than the ligand, EGF. Concanavalin A (Con A) and wheatgerm agglutinin (WGA) had the same effect. EGFR phosphorylation seems to be involved in the transduction signalling for hyposmotically induced taurine release, as suggested by the latter's reduction when EGFR phosphorylation was blocked by 50 μM AG213 or AG112 and, conversely, its potentiation by EGF (200 ng/ml). The relationship between hyposmotically induced taurine efflux and reduced osmolarity showed saturable kinetics, following a sigmoidal function. EGF shifted the relationship to the left, implying an increase in sensitivity to hyposmolarity. EGF increased taurine efflux only marginally under isosmotic conditions. EGF and agglutinins also potentiated the hyposmotically induced release of 86Rb but, in contrast to taurine, the efflux was unaffected by EGFR inhibition. EGF and agglutinins markedly increased 86Rb release under isosmotic conditions. The EGF-evoked isosmotic 86Rb release, together with the hyposmotic efflux, accounted fully for the observed potentiation by EGF, raising the possibility of an overlapping of these two effects, rather than a true potentiation. A link between EGFR, phosphatidylinositide-3-kinase (PI3K) and hyposmotically induced taurine (but not 86Rb) release is suggested by the increase in PI3K activity elicited by hyposmolarity, which was folly prevented by EGFR inhibition, and by a marked reduction of hyposmotically induced taurine (but not 86Rb) release, by wortmannin. The present findings, together with results showing EGF activation of osmosensitive Cl- fluxes implicate EGFR as an important modulator of osmolyte efflux pathways.

Original languageEnglish (US)
Pages (from-to)830-839
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Volume447
Issue number6
DOIs
StatePublished - Mar 1 2004

Fingerprint

Fibroblasts
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Taurine
Phosphorylation
Agglutinins
Phosphotransferases
Concanavalin A
Osmolar Concentration
Modulators
Chemical activation
Fluxes
Ligands
Kinetics

Keywords

  • Cell volume
  • EGFR
  • Osmolyte
  • PI3K
  • Taurine

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Epidermal growth factor receptor is activated by hyposmolarity and is an early signal modulating osmolyte efflux pathways in Swiss 3T3 fibroblasts. / Franco, Rodrigo; Lezama, Ruth; Ordaz, Benito; Pasantes-Morales, Herminia.

In: Pflugers Archiv European Journal of Physiology, Vol. 447, No. 6, 01.03.2004, p. 830-839.

Research output: Contribution to journalArticle

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