Nerve growth factor binds to the 140 kd trk proto-oncogene product and stimulates its association with the src homology domain of phospholipase C gamma 1.
The cellular actions of nerve growth factor (NGF) involve regulation of protein phosphorylation. In PC-12 pheochromocytoma cells, exposure of [125I]NGF followed by crosslinking indicates that the ligand binds to two discreet receptors, the previously described 75 kd protein, as well as the trk proto-oncogene product pp140c-trk. Competition experiments reveal that of the two, pp 140c-trk binds to NGF with higher affinity. Following exposure to NGF, pp140c-trk undergoes a rapid autophosphorylation on tyrosine residues, and concomitantly phosphorylates and associates with phospholipase C gamma 1 (PLC gamma 1), through interaction with its src homology domains. The binding of NGF to pp140c-trk with high affinity, the NGF-dependent homology domains. The binding of NGF to pp140c-trk with high affinity, the NGF-dependent activation of its tyrosine kinase activity and the specific association with the effector molecule, PLC gamma 1, suggests that this is the biologically relevant signaling receptor for NGF.
Ohmichi
M
M
Department of Physiology, University of Michigan School of Medicine, Ann Arbor 48109.
Decker
S J
SJ
Pang
L
L
Saltiel
A R
AR
D000310:Adrenal Gland Neoplasms; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D016391:Genes, src; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D009414:Nerve Growth Factors / Q000378:metabolism*; D010673:Pheochromocytoma; D019000:Phosphotyrosine; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011519:Proto-Oncogenes; D051381:Rats; D020917:Receptor, trkA; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D007527:Isoenzymes; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA; D010738:Type C Phospholipases