Corticotropin (ACTH) inhibits the specific proteolysis of the neuronal phosphoprotein B-50/GAP-43.
The modulatory action of corticotropin (ACTH) on the specific proteolysis of B-50 to B-60 [B-50(41-226)] was investigated using a previously characterized synaptosomal membrane extract [ASP(57-82)] that was highly enriched in B-50, B-50 kinase activity and a B-50 protease. In common with the previously described inhibitory action on B-50 phosphorylation at Ser41, ACTH(1-24) inhibited B-50 proteolysis in a concentration and structurally dependent manner, while ACTH(1-10) and ACTH(11-24) or a combination of both peptides were ineffective. Structural similarities between segments of ACTH(1-24) and B-50(40-55) may explain the inhibitory action of the peptide on B-50 phosphorylation and proteolysis. In addition, calmodulin, which binds to the N-terminus of the dephosphorylated form of the protein, also protected B-50 from degradation.
Zwiers
H
H
Department of Medical Physiology, University of Calgary, Health Sciences Centre, Alberta, Canada.
Coggins
P J
PJ
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D053497:Corticotropin-Like Intermediate Lobe Peptide; D003366:Cosyntropin / Q000494:pharmacology; D003864:Depression, Chemical; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism
D002147:Calmodulin; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; D003366:Cosyntropin; C011393:ACTH (1-10); C034016:ACTH (11-24); D053497:Corticotropin-Like Intermediate Lobe Peptide; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D012697:Serine Endopeptidases