PMID- 16971381
OWN - NLM
STAT- MEDLINE
DCOM- 20070323
LR  - 20091119
IS  - 0959-6658 (Print)
IS  - 0959-6658 (Linking)
VI  - 17
IP  - 1
DP  - 2007 Jan
TI  - Dependence of neurotrophic factor activation of Trk tyrosine kinase receptors on 
      cellular sialidase.
PG  - 10-24
AB  - A direct link between receptor glycosylation and activation following natural 
      ligand interaction has not been observed. Here, we discover a membrane 
      sialidase-controlling mechanism that depends on ligand binding to its receptor to 
      induce enzyme activity which targets and desialylates the receptor and, 
      consequently, causes the induction of receptor dimerization and activation. We 
      also identify a specific sialyl alpha-2,3-linked beta-galactosyl sugar residue of 
      TrkA tyrosine kinase receptor, which is rapidly targeted and hydrolyzed by the 
      sialidase. Trk-expressing cells and primary cortical neurons following 
      stimulation with specific neurotrophic growth factors express a vigorous membrane 
      sialidase activity. Neuraminidase inhibitors, Tamiflu, BCX1812, and BCX1827, 
      block sialidase activity induced by nerve growth factor (NGF) in TrkA-PC12 cells 
      and by brain-derived neurotrophic factor (BDNF) in primary cortical neurons. In 
      contrast, the neuraminidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic 
      acid, specific for plasma membrane ganglioside Neu3 and Neu2 sialidases has no 
      inhibitory effect on NGF-induced pTrkA. The GM1 ganglioside specific cholera 
      toxin subunit B applied to TrkA-PC12 cells has no inhibitory effect on 
      NGF-induced sialidase activity. Neurite outgrowths induced by NGF-treated 
      TrkA-PC12 and BDNF-treated PC12(nnr5) stably transfected with TrkB receptors 
      (TrkB-nnr5) cells are significantly inhibited by Tamiflu. Our results establish a 
      novel mode of regulation of receptor activation by its natural ligand and define 
      a new function for cellular sialidases.
FAU - Woronowicz, Alicja
AU  - Woronowicz A
AD  - Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, 
      Canada.
FAU - Amith, Schammim R
AU  - Amith SR
FAU - De Vusser, Kristof
AU  - De Vusser K
FAU - Laroy, Wouter
AU  - Laroy W
FAU - Contreras, Roland
AU  - Contreras R
FAU - Basta, Sameh
AU  - Basta S
FAU - Szewczuk, Myron R
AU  - Szewczuk MR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060913
PL  - England
TA  - Glycobiology
JT  - Glycobiology
JID - 9104124
RN  - 0 (Asialoglycoproteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 3.2.1.18 (Neuraminidase)
SB  - IM
EIN - Glycobiology. 2007 Oct;17(10):1030
MH  - Animals
MH  - Asialoglycoproteins/chemistry
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Embryo, Mammalian
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Nerve Growth Factors/metabolism/*pharmacology
MH  - Neuraminidase/*metabolism
MH  - Neurons/drug effects/metabolism
MH  - PC12 Cells
MH  - Pregnancy
MH  - Protein Binding
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptor, trkA/chemistry
EDAT- 2006/09/15 09:00
MHDA- 2007/03/24 09:00
CRDT- 2006/09/15 09:00
PHST- 2006/09/15 09:00 [pubmed]
PHST- 2007/03/24 09:00 [medline]
PHST- 2006/09/15 09:00 [entrez]
AID - cwl049 [pii]
AID - 10.1093/glycob/cwl049 [doi]
PST - ppublish
SO  - Glycobiology. 2007 Jan;17(1):10-24. doi: 10.1093/glycob/cwl049. Epub 2006 Sep 13.