The differential regulation of steroidogenic acute regulatory protein-mediated steroidogenesis by type I and type II PKA in MA-10 cells.
Following tropic hormone challenge, steroidogenic tissues utilize PKA to phosphorylate unique subsets of proteins necessary to facilitate steroidogenesis. This includes the PKA-dependent expression and activation of the steroidogenic acute regulatory protein (STAR), which mediates the rate-limiting step of steroidogenesis by inducing the transfer of cholesterol from the outer to the inner mitochondrial membrane. Since both type I and type II PKA are present in steroidogenic tissues, we have utilized cAMP analog pairs that preferentially activate each PKA subtype in order to examine their impact on STAR synthesis and activity. In MA-10 mouse Leydig tumor cells Star gene expression is more dependent upon type I PKA, while the post-transcriptional regulation of STAR appears subject to type II PKA. These experiments delineate the discrete effects that type I and type II PKA exert on STAR-mediated steroidogenesis, and suggest complimentary roles for each subtype in coordinating steroidogenesis.
Dyson
Matthew T
MT
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, United States.
Kowalewski
Mariusz P
MP
Manna
Pulak R
PR
Stocco
Douglas M
DM
D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D054743:Cyclic AMP-Dependent Protein Kinase Type I / Q000235:genetics / Q000378:metabolism*; D054746:Cyclic AMP-Dependent Protein Kinase Type II / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007984:Leydig Cell Tumor; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D000242:Cyclic AMP; D054743:Cyclic AMP-Dependent Protein Kinase Type I; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D048031:JNK Mitogen-Activated Protein Kinases