Inhibition of cGMP-dependent protein kinase by the regulatory subunit of photoreceptor cGMP phosphodiesterase.
cGMP-dependent protein kinases (PKGs) mediate many cellular processes including neuronal signaling. The functional significance of PKG I in neurons is emphasized by recent findings that indicate its broad distribution in the brain and eye. In the photosensitive neurons (photoreceptors), the inhibitory gamma subunit (Pgamma) of the central effector cGMP phosphodiesterase (PDE6) modulates visual signaling through a cooperative binding together with cGMP to the regulatory domains of the PDE6 catalytic subunits. Here, we report that PKG Ialpha is inhibited by Pgamma. Kinase activity assays showed that the maximum inhibition of PKG by Pgamma was similar to that by a specific PKG inhibitor. The N-terminal half (Pgamma1-61) containing a polycationic region was found to be a more potent PKG inhibitor as compared to the full-length molecule, whereas the C-terminus (Pgamma62-87) did not inhibit PKG activity. Pgamma itself was not found to be a phosphorylation substrate of PKG. This finding may provide important insights into the modulations in neurons and other cells.
Guo
Lian-Wang
LW
Department of Pharmacology, University of Wisconsin Medical School, 1300 University Ave, Madison, WI 53706, USA. lianwangguo@facstaff.wisc.edu
Ruoho
Arnold E
AE
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography / Q000379:methods; D002417:Cattle; D003001:Cloning, Molecular / Q000379:methods; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D010786:Photoreceptor Cells / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D021122:Protein Subunits; D017869:Cyclic GMP-Dependent Protein Kinases; D015106:3',5'-Cyclic-GMP Phosphodiesterases