Proteomics

Dataset Information

2

Active kinome in human skeletal muscle insulin resistance


ABSTRACT: Obesity-related insulin resistance (OIR) is one of the main contributors to type 2 diabetes and other metabolic diseases. Protein kinases are implicated in key signaling steps including insulin signaling and glucose metabolism. Molecular mechanisms underlying OIR involving global active kinases remain less understood. Herein, we report findings from an in vivo active kinase profiling study in skeletal muscle from lean control (Lean) and OIR human participants, which identified the 1st active kinome comprised of 54 active protein kinases in human skeletal muscle. The activities of 23 kinases were different in OIR compared to Lean muscle (11 hyper- and 12 hypo-active), while their protein abundance was the same between the two groups. The activities of multiple kinases involved in AMPK and p38 signaling were lower in OIR compared to Lean. On the contrary, multiple kinases in JNK signaling pathway exhibited higher activity in OIR vs. Lean muscle. The kinase-substrate-prediction based on experimental data further confirmed a potential down-regulation of insulin signaling (e.g., inhibited phosphorylation of insulin receptor substrate-1 and AKT1/2). These findings provide a global view of the active kinome in OIR and Lean muscle, pinpoint novel specific impairment in kinase activities in multiple signaling pathways important for skeletal muscle insulin resistance, and provide potential drug targets (i.e., abnormal active kinase) to prevent and/or reverse skeletal muscle insulin resistance in humans.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo sapiens  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Yue Qi  

LAB HEAD: Zhengping Yi

PROVIDER: PXD011909 | Pride | 2020-01-23

REPOSITORIES: Pride

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Publications

Kinome Profiling Reveals Abnormal Activity of Kinases in Skeletal Muscle From Adults With Obesity and Insulin Resistance.

Qi Yue Y   Zhang Xiangmin X   Seyoum Berhane B   Msallaty Zaher Z   Mallisho Abdullah A   Caruso Michael M   Damacharla Divyasri D   Ma Danjun D   Al-Janabi Wissam W   Tagett Rebecca R   Alharbi Majed M   Calme Griffin G   Mestareehi Aktham A   Draghici Sorin S   Abou-Samra Abdul A   Kowluru Anjaneyulu A   Yi Zhengping Z  

The Journal of clinical endocrinology and metabolism 20200301 3


<h4>Context</h4>Obesity-related insulin resistance (OIR) is one of the main contributors to type 2 diabetes and other metabolic diseases. Protein kinases are implicated in insulin signaling and glucose metabolism. Molecular mechanisms underlying OIR involving global kinase activities remain incompletely understood.<h4>Objective</h4>To investigate abnormal kinase activity associated with OIR in human skeletal muscle.<h4>Design</h4>Utilization of stable isotopic labeling-based quantitative proteom  ...[more]

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