Differential feedback regulation of the MAPK cascade underlies the quantitative differences in EGF and NGF signalling in PC12 cells

[摘要]

Although epidermal growth factor (EGF) induces transient activation of Ras and the mitogen-activated protein kinase (MAPK) cascade in PC12 cells, whereas nerve growth factor (NGF) stimulates sustained activation, the basis for these contrasting responses is not known. We have developed a computer simulation of EGF-induced MAPK cascade activation, which provides quantitative evidence that feedback inhibition of the MAPK cascade is the most important factor in determining the duration of cascade activation. Hence, we propose that the observed quantitative differences in EGF and NGF signalling can be accounted for by differential feedback regulation of the MAPK cascade.

[学科分类] 生物化学/生物物理

[关键词] Epidermal growth factor;Nerve growth factor;PC12 cell;Ras;Mitogen-activated protein kinase;Son of sevenless;EGF;epidermal growth factor;NGF;nerve growth factor;MAPK;mitogen-activated protein kinase;ERK;extracellular signal-regulated kinase;MEK;MAPK or ERK kinase;EGFR;EGF receptor;GAP;Ras GTPase activating protein;RTK;receptor tyrosine kinase;Shc;Src homology and collagen domain protein;Grb2;growth factor receptor binding protein 2;SOS;Son of sevenless homologue protein;TrkA;high affinity NGF tyrosine kinase receptor;PTPase;protein tyrosine phosphatase;PP2A;protein phosphatase 2A