tailieunhanh - Báo cáo khoa hoc : Insulin receptor substrate 2 and FoxO3a signalling are involved in E-cadherin expression and transforming growth factor-b1-induced repression in kidney epithelial cells

Insulin receptor substrate (IRS) proteins comprise a family of adaptor molecules that integrate extracellular signals from insulin and other ligands to intracellular effectors such as phosphoinositide 3-kinase and mitogen-activated protein kinase. The predominant forms of IRS protein in humans, IRS1 and IRS2, are widely expressed. | IFEBS Journal Insulin receptor substrate 2 and FoxO3a signalling are involved in E-cadherin expression and transforming growth factor-p1-induced repression in kidney epithelial cells Rosemarie M. Carew1 Marie B. Browne1 Fionnuala B. Hickey1 and Derek P. Brazil2 1 UCD Conway Institute University College Dublin Belfield Ireland 2 Centre for Vision and Vascular Science Schoolof Medicine Dentistry and BiomedicalSciences Queen s University Belfast UK Keywords E-cadherin FoxO transcription factor insulin receptor substrate kidney transforming growth factor-beta Correspondence D. P. Brazil Centre for Vision and Vascular Science School of Medicine Dentistry and BiomedicalSciences Queen s University Belfast Northern Ireland UK Fax 44 28 9063 2699 Tel 44 28 9063 2572 E-mail Received 21 April 2011 revised 7 July 2011 accepted 18 July 2011 doi Insulin receptor substrate IRS proteins comprise a family of adaptor molecules that integrate extracellular signals from insulin and other ligands to intracellular effectors such as phosphoinositide 3-kinase and mitogen-activated protein kinase. The predominant forms of IRS protein in humans IRS1 and IRS2 are widely expressed. Despite structural similarities IRS1 and IRS2 display distinct signalling modalities and mice lacking these proteins present with distinct phenotypes. Transforming growth factor TGF -pi is the primary cytokine shown to induce epithelial-mesenchymal transition. Recent data have demonstrated a role for IRS1 in TGF-pi-induced epithelial-mesenchymal transition in lung epithelial cells. In the present study we report data showing that TGF-pi signals via IRS2 in kidney epithelial cells. Small interfering RNA siRNA -mediated targeting of IRS2 increased E-cadherin expression although it did not alter TGF-pi-mediated E-cadherin repression. Phosphorylation of the downstream target of IRS2 Akt signalling FoxO3a was induced on Ser253 and to a lesser extent on Thr32. .

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