PXD011909

PXD011909 is an original dataset announced via ProteomeXchange.

Title	Active kinome in human skeletal muscle insulin resistance
Description	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.
HostingRepository	PRIDE
AnnounceDate	2020-01-23
AnnouncementXML	Submission_2020-01-22_23:43:45.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yue Qi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-30 08:14:24	ID requested
⏵ 1	2020-01-22 23:48:57	announced

Qi Y, Zhang X, Seyoum B, Msallaty Z, Mallisho A, Caruso M, Damacharla D, Ma D, Al-Janabi W, Tagett R, Alharbi M, Calme G, Mestareehi A, Draghici S, Abou-Samra A, Kowluru A, Yi Z, Kinome Profiling Reveals Abnormal Activity of Kinases in Skeletal Muscle From Adults With Obesity and Insulin Resistance. J Clin Endocrinol Metab, 105(3):644-59(2020) [pubmed]

submitter keyword: Insulin resistance, Quantitative proteomics, Human skeletal muscle, Protein kinase, Active kinome

Zhengping Yi
contact affiliation	Department of Pharmaceutical Sciences - Room 3146, Eugene Applebaum College of Pharmacy/Health Sciences, Wayne State University, 6135 Woodward Ave., Detroit, MI 48202
contact email	Zhengping.yi@wayne.edu
lab head
Yue Qi
contact affiliation	National Cancer Institute/NIH
contact email	andy.qi@nih.gov
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/01/PXD011909

PRIDE project URI

• PRIDE
  1. PXD011909
     1. Label: PRIDE project
     2. Name: Active kinome in human skeletal muscle insulin resistance