NDLI: Network topology determines dynamics of the mammalian MAPK1,2 signaling network: bifan motif regulation of C-Raf and B-Raf isoforms by FGFR and MC1R.

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Network topology determines dynamics of the mammalian MAPK1,2 signaling network: bifan motif regulation of C-Raf and B-Raf isoforms by FGFR and MC1R.

Content Provider	Semantic Scholar
Author	Muller, Melissa Obeyesekere, Mandri Mills, Gordon B. Ram, Prahlad T.
Copyright Year	2008
Abstract	Activation of the fibroblast growth factor (FGFR) and melanocyte stimulating hormone (MC1R) receptors stimulates B-Raf and C-Raf isoforms that regulate the dynamics of MAPK1,2 signaling. Network topology motifs in mammalian cells include feed-forward and feedback loops and bifans where signals from two upstream molecules integrate to modulate the activity of two downstream molecules. We computationally modeled and experimentally tested signal processing in the FGFR/MC1R/B-Raf/C-Raf/MAPK1,2 network in human melanoma cells; identifying 7 regulatory loops and a bifan motif. Signaling from FGFR leads to sustained activation of MAPK1,2, whereas signaling from MC1R results in transient activation of MAPK1,2. The dynamics of MAPK activation depends critically on the expression level and connectivity to C-Raf, which is critical for a sustained MAPK1,2 response. A partially incoherent bifan motif with a feedback loop acts as a logic gate to integrate signals and regulate duration of activation of the MAPK signaling cascade. Further reducing a 106-node ordinary differential equations network encompassing the complete network to a 6-node network encompassing rate-limiting processes sustains the feedback loops and the bifan, providing sufficient information to predict biological responses.
Starting Page	296
Ending Page	302
Page Count	7
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.fasebj.org/content/22/5/1393.full.pdf
PubMed reference number	18171696v1
Alternate Webpage(s)	https://doi.org/10.1096/fj.07-9100com
DOI	10.1096/fj.07-9100com
Journal	FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume Number	22
Issue Number	5
Language	English
Access Restriction	Open
Subject Keyword	Anatomy, Regional Cascade Device Component Fibroblast Growth Factor Receptors Gonadorelin MC1R gene Mammals Protein Domain Protein Isoforms
Content Type	Text
Resource Type	Article

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