Stability Analysis of Time Delay Model of Crosstalk between ERK and STAT5a Interaction

In this paper we investigate the qualitative behavior of a time delay model of the crosstalk between ERK and STAT5. We apply linear approximation to study the time delay model. The influence of some parameters on the dynamics of the model is analyzed analytically and numerically. Our qualitative results show that the model is structurally unstable. Relating this result to the physiological nature of the studied mathematical model, we prove mathematically the appearance of a crosstalk between the signaling pathways ERK and STAT in some cancer cells. This pathology appears when the process of homeostasis is disturbed and it has a non-reverse character.

[1]  Kwang-Hyun Cho,et al.  The dynamic systems approach to control and regulation of intracellular networks , 2005, FEBS letters.

[2]  G. Georgiev,et al.  Dynamical Model of ERK- and STAT- Proteins Interaction , 2006 .

[3]  Bernd Groner,et al.  Mediation of Growth Hormone-dependent Transcriptional Activation by Mammary Gland Factor/Stat 5 (*) , 1995, The Journal of Biological Chemistry.

[4]  Fabio Grizzi,et al.  Cancer Cell International Cancer: Looking for Simplicity and Finding Complexity , 2022 .

[5]  Kwang-Hyun Cho,et al.  Mathematical Modeling of the Influence of RKIP on the ERK Signaling Pathway , 2003, CMSB.

[6]  J. Darnell STATs and gene regulation. , 1997, Science.

[7]  Muffy Calder,et al.  When kinases meet mathematics: the systems biology of MAPK signalling , 2005, FEBS letters.

[8]  David Rakhmilʹevich Merkin,et al.  Introduction to the Theory of Stability , 1996 .

[9]  Carlo Russo,et al.  Theoretical Biology and Medical Modelling Open Access Cancer Initiation and Progression: an Unsimplifiable Complexity , 2022 .

[10]  Tony J. Pircher,et al.  Mitogen-activated protein kinase kinase inhibition decreases growth hormone stimulated transcription mediated by STAT5 , 1997, Molecular and Cellular Endocrinology.

[11]  J A Gustafsson,et al.  Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a. , 1999, Molecular endocrinology.

[12]  C. Clevenger Roles and regulation of stat family transcription factors in human breast cancer. , 2004, The American journal of pathology.

[13]  J. Timmer,et al.  Identification of nucleocytoplasmic cycling as a remote sensor in cellular signaling by databased modeling , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Harrison,et al.  The JAK/STAT signaling pathway , 2004, Journal of Cell Science.

[15]  Ursula Klingmüller,et al.  Modeling the Nonlinear Dynamics of Cellular Signal Transduction , 2004, Int. J. Bifurc. Chaos.

[16]  Steven James Bartlett The Theory of Chaos , 1988 .

[17]  M. Mesarovic,et al.  Feedback dynamics and cell function: Why systems biology is called Systems Biology. , 2005, Molecular bioSystems.

[18]  A. Fuller,et al.  Stability of Motion , 1976, IEEE Transactions on Systems, Man, and Cybernetics.

[19]  O Wolkenhauer,et al.  A systems- and signal-oriented approach to intracellular dynamics. , 2005, Biochemical Society transactions.