PMID- 10209246
OWN - NLM
STAT- MEDLINE
DCOM- 19990526
LR  - 20190831
IS  - 0165-3806 (Print)
IS  - 0165-3806 (Linking)
VI  - 114
IP  - 1
DP  - 1999 Apr 12
TI  - Muscarinic receptor- and phorbol ester-stimulated phosphorylation of protein
      kinase C substrates in adult and neonatal cortical slices.
PG  - 89-98
AB  - The neuron-specific protein B-50 (GAP-43) is a major presynaptic substrate for
      protein kinase C (PKC). Phosphorylation of B-50 by PKC at serine-41 is
      functionally related to signal transduction in association with process outgrowth
      and neurotransmitter release. Thus, it is important to characterize the factors
      which modulate phosphorylation of B-50 by PKC. Phosphoinositide (PI)-coupled
      muscarinic acetylcholine receptor (mAchR) activation would be expected to
      increase PKC activity through production of the second messenger, diacylglycerol.
      To test the hypothesis that activation of mAchR also increases phosphorylation of
      B-50, protein phosphorylation has been examined in cerebral cortical slices in
      response to the cholinergic agonist, carbachol (Cch) in comparison to the phorbol
      ester, 4beta-phorbol 12, 13-dibutyrate (PDB), a known activator of PKC. At short 
      times of incubation with 1 mM Cch, a concentration which maximally activates PI
      metabolism, increased phosphorylation of a group of synaptosomal proteins,
      including B-50 and myristoylated, alanine-rich C kinase substrate (MARCKS), was
      observed. This increase was approximately half of that obtained in response to 1 
      microM PDB. Differing patterns of protein phosphorylation were observed in
      neonatal and adult slices: neonatal samples contained more MARCKS and a PKC
      substrate with a Mr of 46 kDa. Phosphorylation of B-50 and MARCKS was sensitive
      to Cch in both cases. Immunoblotting demonstrated less m1 acetylcholine receptor 
      (the predominant mAchR subtype coupled to PI metabolism in the cortex) in
      neonatal, as compared to adult, synaptosomal fractions. These results are
      consistent with a coupling between mAchR-stimulated PI metabolism and
      PKC-mediated protein phosphorylation that is developmentally regulated.
CI  - Copyright 1999 Elsevier Science B.V.
FAU - Haas, M S
AU  - Haas MS
AD  - Departments of Biochemistry/Molecular Biology and Medicine, Medical College of
      Ohio, Toledo, OH 43614-5809, USA.
FAU - Dokas, L A
AU  - Dokas LA
LA  - eng
GR  - NS 30792/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res Dev Brain Res
JT  - Brain research. Developmental brain research
JID - 8908639
RN  - 0 (Carcinogens)
RN  - 0 (GAP-43 Protein)
RN  - 0 (Muscarinic Agonists)
RN  - 0 (Myristic Acids)
RN  - 0 (Phorbol Esters)
RN  - 0 (Phosphates)
RN  - 0 (Phosphorus Radioisotopes)
RN  - 0 (Receptors, Muscarinic)
RN  - 8Y164V895Y (Carbachol)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Age Factors
MH  - Alanine
MH  - Animals
MH  - Animals, Newborn
MH  - Carbachol/pharmacology
MH  - Carcinogens/*pharmacology
MH  - Cerebral Cortex/chemistry/*enzymology/growth & development
MH  - Enzyme Activation/drug effects
MH  - GAP-43 Protein/metabolism
MH  - Immunoblotting
MH  - Male
MH  - Muscarinic Agonists/pharmacology
MH  - Myristic Acids/metabolism
MH  - Organ Culture Techniques
MH  - Phorbol Esters/*pharmacology
MH  - Phosphates/metabolism
MH  - Phosphorus Radioisotopes
MH  - Phosphorylation
MH  - Protein Kinase C/*metabolism
MH  - Rats
MH  - Receptors, Muscarinic/*physiology
MH  - Substrate Specificity
EDAT- 1999/04/21 00:00
MHDA- 1999/04/21 00:01
CRDT- 1999/04/21 00:00
PHST- 1999/04/21 00:00 [pubmed]
PHST- 1999/04/21 00:01 [medline]
PHST- 1999/04/21 00:00 [entrez]
AID - S0165380699000231 [pii]
AID - 10.1016/s0165-3806(99)00023-1 [doi]
PST - ppublish
SO  - Brain Res Dev Brain Res. 1999 Apr 12;114(1):89-98. doi:
      10.1016/s0165-3806(99)00023-1.