Differential activation of AKT isoforms by growth factors in human myotubes

Author:

Roberts Brandon M.1ORCID,Geddis Alyssa V.1,Matheny Ronald W.12

Affiliation:

1. US Army Research of Environmental Medicine Natick Massachusetts USA

2. Military Operational Medicine Research Program Ft. Detrick Maryland USA

Abstract

AbstractAKT signaling plays a crucial role in muscle physiology, and is activated by stimuli, including insulin, growth factors, and exercise. Three AKT isoforms have been identified in mammals, and they possess both distinct and redundant functions. However, it is currently unknown what the predominant AKT isoform is in primary human skeletal myotubes, and very little is known regarding the effects of insulin and insulin‐like growth factor‐I (IGF‐I) on AKT isoforms activation in human myotubes. Thus, we sought to determine the abundances of each AKT isoform in primary human skeletal myotubes and their responses to insulin or IGF‐I. Analysis of protein lysates by liquid chromatography‐parallel reaction monitoring/mass spectrometry revealed that AKT1 was the most abundant AKT isoform and AKT3 was the least‐abundant isoform. Next, myotubes were treated with either 100 nM insulin or 10 nM IGF‐I for 5, 20, 45, or 60 min. In response to insulin, there was a significant treatment effect on phosphorylation of AKT1 and AKT2, but not AKT3 (p < 0.01). In response to IGF‐I, there was a significant treatment effect on phosphorylation of pan‐AKT at all timepoints compared to control (p < 0.01). Next, we determined how much of the total AKT isoform pool was phosphorylated. For insulin stimulation, AKT1 was significantly higher than AKT2 at 5 min and 60 min posttreatment (p < 0.05 both) and significantly different than AKT3 at all timepoints (p < 0.05). For IGF‐I stimulation, AKT1 was significantly higher than AKT2 at 45 and 60 min posttreatment (p < 0.05 both) and significantly higher than AKT3 at all timepoints (p < 0.05). Our findings reveal the differential phosphorylation patterns among the AKT isoforms and suggest a potential explanation for the regulatory role of AKT1 in skeletal muscle.

Funder

Military Operational Medicine Research Program

Publisher

Wiley

Subject

Physiology (medical),Physiology

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