The mechanism of divalent metal ion chelator induced activation of the 7S nerve growth factor esteropeptidase. Thermodynamics and kinetics of activation

Biochemistry ◽  
1976 ◽  
Vol 15 (17) ◽  
pp. 3696-3703 ◽  
Author(s):  
Scott E. Pattison ◽  
Michael F. Dunn
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Metal Ion ◽  
Divalent Metal ◽  
Nerve Growth ◽  
Thermodynamics And Kinetics ◽  
Divalent Metal Ion ◽  
Kinetics Of

scholarly journals Sustained Signaling by Phospholipase C-γ Mediates Nerve Growth Factor-Triggered Gene Expression

2001 ◽  
Vol 21 (8) ◽  
pp. 2695-2705 ◽  
Author(s):  
Deog-Young Choi ◽  
Juan Jose Toledo-Aral ◽  
Rosalind Segal ◽  
Simon Halegoua
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Binding Site ◽  
Phospholipase C ◽  
Pc12 Cells ◽  
Nerve Growth ◽  
Neuronal Gene ◽  
Intracellular Ca ◽  
Kinetics Of

ABSTRACT In contrast to conventional signaling by growth factors that requires their continual presence, a 1-min pulse of nerve growth factor (NGF) is sufficient to induce electrical excitability in PC12 cells due to induction of the peripheral nerve type 1 (PN1) sodium channel gene. We have investigated the mechanism for this triggered signaling pathway by NGF in PC12 cells. Mutation of TrkA at key autophosphorylation sites indicates an essential role for the phospholipase C-γ (PLC-γ) binding site, but not the Shc binding site, for NGF-triggered induction of PN1. In concordance with results with Trk mutants, drug-mediated inhibition of PLC-γ activity also blocks PN1 induction by NGF. Examination of the kinetics of TrkA autophosphorylation indicates that triggered signaling does not result from sustained activation and autophosphorylation of the TrkA receptor kinase, whose phosphorylation state declines rapidly after NGF removal. Rather, TrkA triggers an unexpectedly prolonged phosphorylation and activation of PLC-γ signaling that is sustained for up to 2 h. Prevention of the elevation of intracellular Ca2+ levels using BAPTA-AM results in a block of PN1 induction by NGF. Sustained signaling by PLC-γ provides a means for differential neuronal gene induction after transient exposure to NGF.

scholarly journals Molecular Kinetics of Nerve Growth Factor Receptor Trafficking and Activation

2002 ◽  
Vol 277 (41) ◽  
pp. 38700-38708 ◽  
Author(s):  
Jérôme Jullien ◽  
Vincent Guili ◽  
Louis F. Reichardt ◽  
Brian B. Rudkin
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Trafficking ◽  
Nerve Growth Factor Receptor ◽  
Nerve Growth ◽  
Kinetics Of
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