Potent human p140-TrkA agonists derived from an anti-receptor monoclonal antibody.
Monoclonal antibody (mAb) 5C3 directed against human p140 TrkA is a structural and functional mimic of nerve growth factor (NGF) and an artificial receptor agonist. mAb 5C3 binds in the NGF-docking site and, like NGF, it promotes TrkA internalization, TrkA and phosphatidylinositol-3 kinase tyrosine phosphorylation, and increased transformation of TrkA-expressing fibroblasts. More important, mAb 5C3 protects human TrkA-expressing cells from apoptotic death in serum-free media. Interestingly, agonistic activity is observed with monomeric F(ab) 5C3 fragments. mAb 5C3 (Kd approximately 2 nM) was used to study features of ligand binding by TrkA and the distribution of TrkA protein in normal human brain.
LeSauteur
L
L
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
Maliartchouk
S
S
Le Jeune
H
H
Quirion
R
R
Saragovi
H U
HU
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001921:Brain / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D009414:Nerve Growth Factors; D011505:Protein-Tyrosine Kinases