cGMP-dependent phosphorylation and degradation of myristoylated alanine-rich C-kinase substrate.
In the mammalian brain, nitric oxide (NO) has been implicated in neuronal signal transmissions. NO stimulates guanylate cyclase to increase intracellular cGMP, which in turn activates cGMP-dependent protein kinases (PKG), but the targets of PKG in the brain have not fully been understood. In this study, we examined cGMP-dependent phosphorylation of proteins in rat brain and found that one of the possible substrates was myristoylated alanine-rich C-kinase substrate (MARCKS), an actin-binding membrane-associated protein that regulates cell adhesion. In addition, possible degradation products of MARCKS were observed after transfection of PKG or stimulation with 8pCPT-cGMP. Western blot analysis showed that the MARCKS protein levels were decreased when the cells were stimulated with 8pCPT-cGMP. These results suggest that MARCKS is a target of PKG, and PKG-dependent phosphorylation of MARCKS results in its degradation to reduce its protein levels in the cells.
Matsubara
Toshiya
T
Division of Protein Metabolism, Institute for Protein Research, Osaka University 3-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
Okumura
Nobuaki
N
Okumura
Akiko
A
Nagai
Katsuya
K
D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009569:Nitric Oxide / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013379:Substrate Specificity
D047908:Intracellular Signaling Peptides and Proteins; C000619711:Marcks protein, mouse; C000619712:Marcks protein, rat; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP