TGF-beta 1 modulates EGF-stimulated phosphatidylinositol 3-kinase activity in human airway smooth muscle cells.

The American Journal of Physiology
V P KrymskayaR A Panettieri

Abstract

Regulation of phosphatidylinositol (PI) 3-kinase plays an important role in modulating cellular function. We have previously shown that transforming growth factor (TGF)-beta 1 inhibited epidermal growth factor (EGF)-induced human airway smooth muscle (hASM) cell proliferation and that PI 3-kinase activation is a necessary signaling event in mitogen-induced hASM cell growth. In this study, we postulated that TGF-beta 1 may modulate EGF-induced PI 3-kinase activation. To date, no study has examined the effects of TGF-beta 1 on PI 3-kinase activity. In cultured hASM cells, EGF induced a 5.7 +/- 1.2-fold activation of PI 3-kinase compared with diluent-treated cells. Although TGF-beta 1 alone did not alter PI 3-kinase activation, TGF-beta 1 markedly enhanced EGF-induced PI 3-kinase activity, with a 16.6 +/- 1.9-fold increase over control cells treated with diluent alone. EGF significantly increased the association of PI 3-kinase with tyrosine phosphorylated proteins, and TGF-beta 1 pretreatment before EGF stimulation apparently did not alter this association. Interestingly, TGF-beta 1 did not modulate EGF-induced p70 S6 kinase activity, which is important for the progression of cells from the G0 to the G1 phase of the cell cycle. Im...Continue Reading

Citations

Aug 2, 2002·American Journal of Respiratory Cell and Molecular Biology·Kristen PageMarc B Hershenson
Mar 5, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Vera P KrymskayaReynold A Panettieri
Mar 11, 2010·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·S MatsukuraM Adachi
Jul 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Elena A GoncharovaVera P Krymskaya
Nov 28, 2007·Annual Review of Pathology·Marc B HershensonJulian Solway
Apr 13, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Elena A GoncharovaVera P Krymskaya
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May 23, 2008·American Journal of Physiology. Renal Physiology·Jayesh J KattlaDerek P Brazil
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