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Molecular and Cellular Biology, July 2007, p. 5172-5183, Vol. 27, No. 14
0270-7306/07/$08.00+0     doi:10.1128/MCB.02298-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Myosin 5a Is an Insulin-Stimulated Akt2 (Protein Kinase Bß) Substrate Modulating GLUT4 Vesicle Translocation{triangledown}

Takeshi Yoshizaki, Takeshi Imamura, Jennie L. Babendure, Juu-Chin Lu, Noriyuki Sonoda, and Jerrold M. Olefsky*

Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, 9500 Gilman Dr., La Jolla, California 92093

Received 8 December 2006/ Returned for modification 31 January 2007/ Accepted 7 May 2007

Phosphatidylinositol 3-kinase activation of Akt signaling is critical to insulin-stimulated glucose transport and GLUT4 translocation. However, the downstream signaling events following Akt activation which mediate glucose transport stimulation remain relatively unknown. Here we identify an Akt consensus phosphorylation motif in the actin-based motor protein myosin 5a and show that insulin stimulation leads to phosphorylation of myosin 5a at serine 1650. This Akt-mediated phosphorylation event enhances the ability of myosin 5a to interact with the actin cytoskeleton. Small interfering RNA-induced inhibition of myosin 5a and expression of dominant-negative myosin 5a attenuate insulin-stimulated glucose transport and GLUT4 translocation. Furthermore, knockdown of Akt2 or expression of dominant-negative Akt (DN-Akt) abolished insulin-stimulated phosphorylation of myosin 5a, inhibited myosin 5a binding to actin, and blocked insulin-stimulated glucose transport. Taken together, these data indicate that myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4 vesicles along actin to the cell surface.

* Corresponding author. Mailing address: Department of Medicine (0673), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0673. Phone: (858) 534-6651. Fax: (858) 534-6653. E-mail: jolefsky{at}ucsd.edu

{triangledown} Published ahead of print on 21 May 2007.

Molecular and Cellular Biology, July 2007, p. 5172-5183, Vol. 27, No. 14
0270-7306/07/$08.00+0     doi:10.1128/MCB.02298-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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