Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.21 (
CPT
)
4,580
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It has been proposed previously that the sustained activation of mitogen-activated protein kinase may be necessary for the differentiation of PC12 cells. Differentiation of PC12 cells is induced by many extracellular agonists including
nerve growth factor
(
NGF
) and cyclicAMP analogues, but not epidermal growth factor (EGF), insulin or phorbol esters. Our results demonstrate that: (i) 8-(4-chlorophenylthio)-cyclicAMP (
CPT
-cAMP) activates MAP kinase; this raises the possibility that the MAP kinase pathway may be activated by agents that act through adenylate cyclase; (ii)
NGF
and
CPT
-cAMP as well as phorbol esters promote sustained activation of MAP kinase. This suggests that while sustained MAP kinase activation may be associated with differentiation it may not be sufficient, and that other as yet unidentified parallel pathways may be involved.
...
PMID:Differentiation of PC12 cells in response to a cAMP analogue is accompanied by sustained activation of mitogen-activated protein kinase. Comparison with the effects of insulin, growth factors and phorbol esters. 830 83
The
nerve growth factor
(
NGF
) pathway has been shown to play a key role in pain treatment. Recently, a systems pharmacology model has been proposed that can aid in the identification and validation of drug targets in the
NGF
pathway. However, this model did not include the role of the p75 receptor, which modulates the signaling of
NGF
through the tropomyosin receptor kinase A (TrkA). The precise mechanism of the interaction between these two receptors has not been completely elucidated, and we therefore adopted a systems pharmacology modeling approach to gain understanding of the effect of p75 on the dynamics of
NGF
signal transduction. Specifically, models were developed for the so-called heterodimer and for the ligand-passing hypotheses. We used the model to compare the effect of inhibition of
NGF
and TrkA and its implication for drug discovery and development for pain treatment.
CPT
Pharmacometrics Syst Pharmacol 2014 Dec 03
PMID:Systems Pharmacology of the NGF Signaling Through p75 and TrkA Receptors. 2547 Jan 84