Linked Life Data

21411748

Source:http://linkedlifedata.com/resource/pubmed/id/21411748

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-5-30
pubmed:abstractText
Signaling by TrkA and TrkB receptor tyrosine kinase is required for peripheral neuron survival. TrkA and TrkB signaling is facilitated by the p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor (TNF) receptor superfamily, through mechanisms that remain obscure. Here, we demonstrate that TrkA and TrkB induces MEK-dependent phosphorylation of the transmembrane cysteine protease ADAM17 (a disintegrin and metalloprotease 17) at the intracellular residue threonine 735. Phosphorylation at this site activates ADAM17 and causes cleavage of p75NTR and production of the receptors' intracellular domain (p75NTR(ICD)) in PC12 cells and in primary cerebellar granule neurons. We show that Trk-induced ADAM17 phosphorylation and generation of the p75NTR(ICD) is required for neurotrophin-induced Erk and Akt activation and for neurotrophin-dependent survival signaling. Survival of PC12 cells maintained in 10 ng/ml nerve growth factor drops by 47% in cells depleted of ADAM17; this survival deficit is resolved if the p75NTR(ICD) is overexpressed in the ADAM17 depleted cells. These studies identify a novel signaling circuit in which Trk activates ADAM17-dependent p75NTR(ICD) production to feedback to sustain Trk signaling and Trk-dependent survival.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2061-70
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Trk-dependent ADAM17 activation facilitates neurotrophin survival signaling.
pubmed:affiliation
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University St., Montreal, QC, Canada, H3A 2B4.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't