PMID- 10440735
OWN - NLM
STAT- MEDLINE
DCOM- 19991220
LR  - 20131121
IS  - 0022-3034 (Print)
IS  - 0022-3034 (Linking)
VI  - 40
IP  - 3
DP  - 1999 Sep 5
TI  - Agrin-independent activation of the agrin signal transduction pathway.
PG  - 356-65
AB  - The neural factor agrin induces the aggregation of acetylcholine receptors 
      (AChRs) and other synaptic molecules on cultured myotubes. This aggregating 
      activity can be mimicked by experimental manipulations that include treatment 
      with neuraminidase or elevated calcium. We report evidence that neuraminidase and 
      calcium act through the agrin signal transduction pathway. The effects of 
      neuraminidase and calcium on AChR clustering are additive with that of agrin at 
      low concentrations and cosaturating at high concentrations. In addition, like 
      agrin, both neuraminidase and calcium cause rapid tyrosine phosphorylation of the 
      muscle-specific kinase (MuSK) and the AChR-beta subunit. Our results argue that 
      all three agents act directly on components of the same signal transduction 
      complex. We suggest that sialic acids on components of the complex inhibit 
      interactions necessary for signal transduction and that disinhibition can result 
      in activation. In such a model, agrin could activate signal transduction by 
      disinhibition or by circumventing the inhibition.
CI  - Copyright 1999 John Wiley & Sons, Inc.
FAU - Grow, W A
AU  - Grow WA
AD  - Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 
      85724-5044, USA.
FAU - Ferns, M
AU  - Ferns M
FAU - Gordon, H
AU  - Gordon H
LA  - eng
GR  - 1 T32 N50763/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurobiol
JT  - Journal of neurobiology
JID - 0213640
RN  - 0 (Agrin)
RN  - 0 (Calcium Channels)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 3.2.1.18 (Neuraminidase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Agrin/*metabolism
MH  - Animals
MH  - Calcium/pharmacology
MH  - Calcium Channels/drug effects
MH  - Calcium Signaling/physiology
MH  - Cell Aggregation/drug effects
MH  - Cell Communication/drug effects
MH  - Cells, Cultured
MH  - Molecular Mimicry/drug effects
MH  - Neuraminidase/pharmacology
MH  - Phosphorylation/drug effects
MH  - Protein-Tyrosine Kinases/drug effects
MH  - Receptors, Cholinergic/drug effects
MH  - Signal Transduction/*drug effects
EDAT- 1999/08/10 00:00
MHDA- 1999/08/10 00:01
CRDT- 1999/08/10 00:00
PHST- 1999/08/10 00:00 [pubmed]
PHST- 1999/08/10 00:01 [medline]
PHST- 1999/08/10 00:00 [entrez]
AID - 10.1002/(SICI)1097-4695(19990905)40:3<356::AID-NEU7>3.0.CO;2-F [pii]
PST - ppublish
SO  - J Neurobiol. 1999 Sep 5;40(3):356-65.