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Originally published as MBC in Press, 10.1091/mbc.E05-10-0969 on March 8, 2006

Vol. 17, Issue 5, 2322-2330, May 2006

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Protein Kinase C{zeta} Mediates Insulin-induced Glucose Transport through Actin Remodeling in L6 Muscle Cells

Li-Zhong Liu * {dagger}, Hai-Lu Zhao {dagger}, Jin Zuo *, Stanley K.S. Ho {dagger}, Juliana C.N. Chan {dagger}, Yan Meng *, Fu-De Fang *, and Peter C.Y. Tong {dagger}

* Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 100005 Beijing, China; {dagger} Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

Submitted October 24, 2005; Revised January 23, 2006; Accepted March 1, 2006
Monitoring Editor: Carl-Henrik Heldin

Protein kinase C (PKC) {zeta} has been implicated in insulin-induced glucose uptake in skeletal muscle cell, although the underlying mechanism remains unknown. In this study, we investigated the effect of PKC{zeta} on actin remodeling and glucose transport in differentiated rat L6 muscle cells expressing myc-tagged glucose transporter 4 (GLUT4). On insulin stimulation, PKC{zeta} translocated from low-density microsomes to plasma membrane accompanied by increase in GLUT4 translocation and glucose uptake. Z-scan confocal microscopy revealed a spatial colocalization of relocated PKC{zeta} with the small GTPase Rac-1, actin, and GLUT4 after insulin stimulation. The insulin-mediated colocalization, PKC{zeta} distribution, GLUT4 translocation, and glucose uptake were inhibited by wortmannin and cell-permeable PKC{zeta} pseudosubstrate peptide. In stable transfected cells, overexpression of PKC{zeta} caused an insulin-like effect on actin remodeling accompanied by a 2.1-fold increase in GLUT4 translocation and 1.7-fold increase in glucose uptake in the absence of insulin. The effects of PKC{zeta} overexpression were abolished by cell-permeable PKC{zeta} pseudosubstrate peptide, but not wortmannin. Transient transfection of constitutively active Rac-1 recruited PKC{zeta} to new structures resembling actin remodeling, whereas dominant negative Rac-1 prevented the insulin-mediated PKC{zeta} translocation. Together, these results suggest that PKC{zeta} mediates insulin effect on glucose transport through actin remodeling in muscle cells.


This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-10-0969) on March 8, 2006.

Address correspondence to: Peter C.Y. Tong (ptong{at}cuhk.edu.hk), Fu-De Fang (fangfd{at}public3.bta.net.cn), or Yan Meng (ymengsmile{at}yahoo.com).




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