1. Academic Validation
  2. CaMKII and Kalirin, a Rac1-GEF, regulate Akt phosphorylation involved in contraction-induced glucose uptake in skeletal muscle cells

CaMKII and Kalirin, a Rac1-GEF, regulate Akt phosphorylation involved in contraction-induced glucose uptake in skeletal muscle cells

  • Biochem Biophys Res Commun. 2022 Jun 25;610:170-175. doi: 10.1016/j.bbrc.2022.03.152.
Sasa Liu 1 Juan Zhang 1 Rui Qi 1 Bangli Deng 2 Yuge Ni 1 Chang Zhang 1 Wenyan Niu 3
Affiliations

Affiliations

  • 1 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Department of Pharmacy, General Hospital, Tianjin Medical University, Tianjin, 300070, China.
  • 2 NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China.
  • 3 Department of Immunology, Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Department of Pharmacy, General Hospital, Tianjin Medical University, Tianjin, 300070, China; NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China. Electronic address: wniu@tmu.edu.cn.
Abstract

Rac1 plays an important role in contraction-stimulated muscle glucose uptake, but the mechanism is not fully elucidated. We previously identified Rac1-dependent activation of Akt played a partial role in contraction-stimulated GLUT4 translocation to the cell surface of C2C12 myotubes. Recognizing that contraction activates CaMKII in muscle and CaMKII is known to regulate Rac1 activity in other systems, here we investigated the relationship between CaMKII, Akt and contraction-stimulated glucose uptake. Expression of a constitutively-active mutant of CaMKIIδ stimulated Akt phosphorylation that was inhibited by Rac1 inhibitor II. C2C12 myotubes were contracted by electrical pulse stimulation (EPS). We observed the CaMKII inhibitor, KN-93 and CaMKIIδ siRNA-mediated knockdown, reduced EPS-induced Akt phosphorylation in C2C12 myotubes. ITX3, an inhibitor of the Rac-GTPase Kalirin and Kalirin siRNA-mediated knockdown reduced EPS-stimulated Akt phosphorylation in myotubes. In addition, the Akt Inhibitor MK2206 partly reduced EPS-stimulated glucose uptake without simultaneously affecting CaMKII phosphorylation and Kalirin protein abundance. Our findings demonstrate EPS leads to Akt activation through a CaMKII-Kalirin-Rac1 signaling pathway and partly regulates contraction-stimulated glucose uptake in muscle cells.

Keywords

Akt1/2; Calcium/calmodulin-dependent protein kinase II; Contraction; Glucose uptake; Kalirin; Rac1.

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