PINCH Proteins Regulate Cardiac Contractility by Modulating Integrin-Linked Kinase-Protein Kinase B Signaling

• DOI: 10.1128/mcb.05269-11
• Publication Date: 2011-06-14T03:15:24Z
• Authors: Benjamin Meder; Inken G. Huttner; Farbod Sedaghat-H...; Steffen Just; Tillman Dahme; Karen S. Frese; Britta Vogel; Doreen Köhler; Wanda Kloos; Jessica Rudloff; Sabine Marquart; Hugo A. Katus; Wolfgang Rottbauer
• Keywords: Integrin-linked kinase; Contractility

Integrin-linked kinase (ILK) is an essential component of the cardiac mechanical stretch sensor and bound in a protein complex with parvin PINCH proteins, so-called ILK-PINCH-parvin (IPP) complex. We have recently shown that inactivation ILK or β-parvin activity leads to heart failure zebrafish via reduced B (PKB/Akt) activation. Here, we show proteins localize at sarcomeric Z disks costameres skeletal muscle. To investigate vivo role for IPP stability PKB signaling within vertebrate heart, inactivated PINCH1 PINCH2 zebrafish. Inactivation either isoform independently instability ILK, loss stretch-responsive anf vegf expression, progressive failure. The predominant cause morphants seems be activity, since phosphorylation serine 473 significantly PINCH-deficient hearts overexpression constitutively active reconstitutes function morphants. These findings highlight controlling contractility by granting IPP/PKB-mediated signaling.