Browse > Article

Kinetic Analysis of the MAPK and PI3K/Akt Signaling Pathways  

Suresh, Babu CV (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology)
Babar, Sheikh Md. Enayetul (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology)
Song, Eun Joo (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology)
Oh, Eulsik (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology)
Yoo, Young Sook (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology)
Publication Information
Molecules and Cells / v.25, no.3, 2008 , pp. 397-406 More about this Journal
Abstract
Computational modeling of signal transduction is currently attracting much attention as it can promote the understanding of complex signal transduction mechanisms. Although several mathematical models have been used to examine signaling pathways, little attention has been given to crosstalk mechanisms. In this study, an attempt was made to develop a computational model for the pathways involving growth-factor-mediated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase/protein kinase B (PI3K/Akt). In addition, the dynamics of the protein activities were analyzed based on a set of kinetic data. The simulation approach integrates the information on several levels and predicts systems behavior. The in-silico analysis conducted revealed that the Raf and Akt pathways act independently.
Keywords
Biochemical Pathway; Computational Modeling; MAPK; PI3K/Akt; Signal Transduction; Systems Biology;
Citations & Related Records

Times Cited By Web Of Science : 3  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Schoeberl, B., Eichler-Jonsson, C., Gilles, E.D., and Muller, G. (2002). Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Nat. Biotechnol. 20, 370-375   DOI   ScienceOn
2 Ugi, S., Imamura, T., Maegawa, H., Egawa, K., Yoshizaki, T., Shi, K., Obata, T., Ebina, Y., Kashiwagi, A., and Olefsky, J.M. (2004). Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (Protein Kinase B) activity in 3T3-L1 adipocytes. Mol. Cell. Biol. 24, 8778-8789   DOI   ScienceOn
3 Van Kanegan, M.J., Adams, D.G., Wadzinski, B.E., and Strack, S. (2005). Distinct protein phosphatase 2A heterotrimers modulate growth factor signaling to extracellular signalregulated kinases and Akt. J. Biol. Chem. 280, 36029-36036   DOI   ScienceOn
4 Wells, A. (2000). The epidermal growth factor receptor (EGFR)- a new target in cancer therapy. Signal 1, 4-11
5 Chan, T.O., Rittenhouse, S.E., and Tsichlis, P.N. (1999). Akt/ PKB and other D3 phosphoinositide-regulated kinases: Kinase activation by phosphoinositide-dependent phosphorylation. Annu. Rev. Biochem. 68, 965-1014   DOI   ScienceOn
6 Chiu, D., Ma, K., Scott, A., and Duronio, V. (2005). Acute activation of Erk1/Erk2 and protein kinase B/akt proceed by independent pathways in multiple cell types. FEBS J. 272, 4372-4384   DOI   ScienceOn
7 Cummings, A., and Kavlock, R.A. (2005). Systems biology approach to developmental toxicology. Reprod. Toxicol. 19, 281-290   DOI   ScienceOn
8 Ferby, I.M., Waga, I., Sakanaka, C., Kume, K., and Shimizu, T. (1994). Wortmannin inhibits mitogen-activated protein kinase activation induced by platelet-activating factor in guinea pig neutrophils. J. Biol. Chem. 269, 30485-30488
9 Liu, E.T. (2005). Systems biology, integrative biology, predictive biology. Cell 121, 505-506   DOI   ScienceOn
10 Mendes, P. (1997). Biochemistry by numbers: simulation of biochemical pathways with Gepasi 3. Trends. Biochem. Sci. 9, 361-363
11 Nicholson, J.K. (2006). Global systems biology, personalized medicine and molecular epidemiology. Mol. Syst. Biol. 2, 52
12 Sasagawa, S., Ozaki, Y., Fujita, K., and Kuroda, S. (2005). Prediction and validation of the distinct dynamics of transient and sustained ERK activation. Nat. Cell Biol. 7, 365-373   DOI   ScienceOn
13 von Gise, A., Lorenz, P., Wellbrock, C., Hemmings, B., Berberich- Siebelt, F., Rapp, U.R., and Troppmair, J. (2001). Apoptosis suppression by Raf-1 and MEK1 requires MEKand phosphatidylinositol 3-kinase-dependent signals. Mol. Cell. Biol. 21, 2324-2336   DOI   ScienceOn
14 Wennstrom, S., and Downward, J. (1999). Role of phosphoinositide 3-kinase in activation of Ras and mitogen-activated protein kinase by epidermal growth factor. Mol. Cell. Biol. 19, 4279-4288   DOI
15 King, W.G., Mattaliano, M.D., Chan, T.O., Tsichlis, P.N., and Brugge, J.S. (1997). Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation. Mol. Cell. Biol. 17, 4406-4418   DOI
16 Cho, S., Park, S.G., Lee, D.H., and Park, B.C. (2004). Proteinprotein interaction networks: from interactions to networks. J. Biochem. Mol. Biol. 37, 45-52
17 Rommel, C., Clarke, B.A., Zimmermann, S., Nuñez, L., Rossman, R., Reid, K., Moelling, K., Yancopoulos, G.D., and Glass, D.J. (1999). Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt. Science 286, 1738-1741   DOI
18 Kitano, H. (2002). Computational systems biology. Nature 420, 206-210   DOI   ScienceOn
19 Cho, K.H., and Wolkenhauer, O. (2003). Analysis and modelling of signal transduction pathways in systems biology. Biochem. Soc. Trans. 31, 1503-1509   DOI
20 Kim, A.H., Khursigara, G., Sun, X., Franke, T.F., and Chao, M.V. (2001). Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol. Cell. Biol. 21, 893-901   DOI   ScienceOn
21 Suresh Babu, C.V., Yoon, S., Nam, H.-S., and Yoo, Y.S. (2004). Simulation and sensitivity analysis of phosphorylation of EGFR signal transduction pathway in PC12 cell model. Sys. Biol. 1, 213-221   DOI   ScienceOn
22 Ivaska, J., Nissinen, L., Immonen, N., Eriksson, J.E., Kähäri, V.M., and Heino, J. (2002). Integrin ${\alpha} 2{\beta}1$ promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase $3{\beta}$. Mol. Cell. Biol. 22, 1352-1359   DOI
23 Tenzer, A., Zingg, D., Rocha, S., Hemmings, B., Fabbro, D., Glanzmann, C., Schubiger, P.A., Bodis, S., and Pruschy, M. (2001). The phosphatidylinositide 3′-kinase/Akt survival pathway is a target for the anticancer and radiosensitizing agent pkc412, an inhibitor of protein kinase C. Cancer Res. 61, 8203-8210
24 Marshall, C.J.S. (1995). Pecificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signalregulated kinase activation. Cell 80, 179-185   DOI   ScienceOn
25 Abraham, D., Podar, K., Pacher, M., Kubicek, M., Welzel, N., Hemmings, B.A., Dilworth, S.M., Mischak, H., Kolch, W., and Baccarini, M. (2000). Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. J. Biol. Chem. 275, 22300-22304   DOI   ScienceOn
26 Lopez-Llasaca, M., Crespo, P., Pellicci, P.G., Gutkind, J.S., and Wetzker, R. (1997). Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase. Science 275, 394-397   DOI   ScienceOn
27 Moelling, K., Schad, K., Bosse, M., Zimmermann, S., and Schweneker, M. (2002). Regulation of Raf-Akt cross-talk. J. Biol. Chem. 277, 31099-31106   DOI   ScienceOn
28 Vanhaesebroeck, B., and Waterfield, M.D. (1999). Signaling by distinct classes of phosphoinositide 3-kinases. Exp. Cell Res. 253, 239-254   DOI   ScienceOn
29 Yamada, S., Taketomi, T., and Yoshimura, A. (2004). Model analysis of difference between EGF pathway and FGF pathway. Biochem. Biophys. Res. Commun. 314, 1113-1120   DOI   ScienceOn
30 Rajasethupathy, P., Vayttaden, S.J., and Bhalla, U.S. (2005). Systems modeling: a pathway to drug discovery. Curr. Opin. Chem. Biol. 9, 400-406   DOI   ScienceOn
31 Qiu, D., Mao, L., Kikuchi, S., and Tomita, M. (2004). Sustained MAPK activation is dependent on continual NGF receptor regeneration. Dev. Growth Differ. 46, 393-403   DOI   ScienceOn
32 Sutor, S.L., Vroman, B.T., Armstrong, E.A.R., Abraham, T., and Karnitz, L.M. (1999). A phosphatidylinositol 3-kinasedependent pathway that differentially regulates c-Raf and ARaf. J. Biol. Chem. 274, 7002-7010   DOI   ScienceOn
33 Tuttle, R.L., Gill, N.S., Pugh, W., Lee, J.P., Koeberlein, B., Furth, E.E., Polonsky, K.S., Naji, A., and Birnbaum, M.J. (2001). Regulation of pancreatic ${\beta}$-cell growth and survival by the serine/threonine protein kinase Akt1/$PKB{\alpha}$. Nat. Med. 7, 1133-1137   DOI   ScienceOn
34 Mendes, P. (1993). GEPASI: a software package for modelling the dynamics, steady states and control of biochemical and other systems. Comput. Appl. Biosci. 5, 563-571
35 Zimmermann, S., and Moelling, K. (1999). Phosphorylation and regulation of Raf by Akt (protein kinase B). Science 286, 1741-1744   DOI   ScienceOn
36 Butcher, E.C., Berg, E.L., and Kunkel, E.J. (2000). Systems biology in drug discovery. (2004). Nat. Biotechnol. 22, 1253-1259   DOI   ScienceOn
37 Hatakeyama, M., Kimura, S., Naka, T., Kawasaki, T., Yumoto, N., Ichikawa, M., Kim, J.H., Saito, K., Saeki, M., Shirouzu, M., et al. (2003). A computational model on the modulation of mitogen-activated protein kinase (MAPK) and Akt pathways in heregulin-induced ErbB signaling. Biochem. J. 373, 451-463   DOI   ScienceOn
38 Gerhardt, C.C., Gros, J., Strosberg, A.D., and Issad, T. (1999). Stimulation of the extracellular signal-regulated kinase 1/2 pathway by human Beta-3 adrenergic receptor: new pharmacological profile and mechanism of activation. Mol. Pharmacol. 55, 255-262   DOI
39 Wixler, V., Smola, U., Schuler, M., and Rapp, U. (1996). Differential regulation of Raf isozymes by growth versus differentiation inducing factors in PC12 pheochromocytoma cells. FEBS Lett. 385, 131-137
40 Carbone, D.P. (2003). Epidermal growth factor receptor overexpression: The importance of context. J. Clin. Oncol. 21, 4268-4269   DOI   ScienceOn
41 Takahashi-Tezuka, M., Yoshida, Y., Fukada, T., Ohtani, T., Yamanaka, Y., Nishida, K., Nakajima, K., Hibi, M., and Hirano, T. (1998). Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen activated protein kinase. Mol. Cell. Biol. 18, 4109-4117   DOI
42 Kao, S., Jaiswal, R.K., Kolch, W., and Gary, E. (2001). Identification of the mechanisms regulating the differential activation of the MAPK cascade by epidermal growth factor and nerve growth factor in PC12 cells. J. Biol. Chem. 276, 18169-8177   DOI   ScienceOn
43 McCubrey, J.A., Leem, J.T., Steelman, L.S., Blalock, W.L., Moye, P.W., Chang, F., Pearce, M., Shelton, J.G., White, M.K., Franklin, R.A., et al. (2001). Interactions between the PI3K and Raf signaling pathways can result in the transformation of hematopoietic cells. Cancer Detect. Prev. 25, 375-393
44 Yamada, S., Shiono, S., Joo, A., and Yoshimura, A. (2003). Control mechanism of JAK/STAT signal transduction pathway. FEBS Lett. 534, 190-196   DOI   ScienceOn
45 Oshima, M., Sithanandam, G., Rapp, U.P., and Guroff, G. (1991). The phosphorylation and activation of B-raf in PC12 cells stimulated by nerve growth factor. J. Biol. Chem. 266, 23753-23760
46 Zi, Z., Cho, K.H., Sung, M.H., Xia, X., Zheng, J., and Sun, Z. (2005). In silico identification of the key components and steps in IFN-gamma induced JAK-STAT signaling pathway. FEBS Lett. 579, 1101-1108   DOI   ScienceOn
47 Andjelkovic, M., Maira, S.M., Cron, P., Parker, P.J., and Hemmings, B.A. (1999). Domain swapping used to investigate the mechanism of protein kinase B regulation by 3-phosphoinositide- dependent protein kinase 1and Ser473 kinase. Mol. Cell. Biol. 19, 5061-5072   DOI
48 Kalisch, B.E., Demeris, C.S., Ishak, M., and Rylett, R.J. (2003). Modulation of nerve growth factor-induced activation of MAP kinase in PC12 cells by inhibitors of nitric oxide synthase. J. Neurochem. 87, 1321-1332   DOI   ScienceOn
49 Newman, J.R., and Weissman, J.S. (2006). Systems biology: many things from one. Nature 444, 561-562   DOI   ScienceOn
50 Hao, N., Behar, M., Elston, T.C., and Dohlman, H.G. (2007). Systems biology analysis of G protein and MAP kinase signaling in yeast. Oncogene 26, 3245-3266
51 Tanke, H.J. (2007). Genomics and proteomics: the potential role of oral diagnostics. Ann. NY Acad. Sci. 1098, 330-334   DOI   ScienceOn