Activation of atypical protein kinase Czeta toward TC10 is regulated by high-fat diet and aerobic exercise in skeletal muscle.
We determined whether sustained aerobic exercise reverses high-fat diet-induced impairments in the c-Cbl associated protein (CAP)/Casitas b-lineage lymphoma (c-Cbl) signaling cascade in rodent skeletal muscle. Sprague-Dawley rats were placed into either control (n = 16) or high-fat-fed (n = 32) diet groups for 4 weeks. During a subsequent 4-week experimental period, 16 high-fat-fed rats remained sedentary, 16 high-fat-fed rats completed 4 weeks of exercise training, and control animals were sedentary and remained on the control diet. After the intervention period, animals were subjected to hind limb perfusions in the presence (n = 8 per group) or absence (n = 8 per group) of insulin. In the plasma membrane fractions, neither high-fat feeding nor exercise training altered adaptor protein with PH and SH2 domains, (APS), c-Cbl, or TC10 protein concentrations. In contrast, CAP protein concentration and insulin-stimulated plasma membrane c-Cbl tyrosine phosphorylation were reduced by high-fat feeding; but exercise training reversed these impairments. Of note was that insulin-stimulated atypical protein kinase Czeta kinase activity toward TC10 was reduced by high-fat feeding but normalized by exercise training. We conclude that sustained (4 weeks) exercise training can reverse high-fat diet-induced impairments on the CAP/c-Cbl pathway in high-fat-fed rodent skeletal muscle. We also provide the first evidence that the CAP/c-Cbl insulin signaling cascade in skeletal muscle may directly interact with components of the classic (phosphoinositide 3-kinase dependent) insulin signaling cascade.
Saito
Misato
M
Exercise Biochemistry Laboratory, Department of Kinesiology, California State University Northridge, CA 91330-8287, USA.
Lessard
S J
SJ
Rivas
Donato A
DA
Reeder
Donald W
DW
Hawley
John A
JA
Yaspelkis
Ben B
BB
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000097:blood / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D004041:Dietary Fats; D007328:Insulin; D007527:Isoenzymes; D008565:Membrane Proteins; D011493:Protein Kinase C; D050721:Proto-Oncogene Proteins c-cbl; D013912:Threonine; D014443:Tyrosine; D020741:rho GTP-Binding Proteins; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta; C488162:Sh2b2 protein, rat; C106354:flotillins; C503262:Rhoq protein, rat