Computational prediction and analysis of impact of the cross-talks between JNK and P38 kinase cascades.

Pandurangan Sundaramurthy,Ramanathan Sowdhamini,Sunita Gakkhar

doi:10.6026/97320630003250

Abstract

Signal transduction is a complex protein signaling process with a rich network of multifunctional interactions that occur in a non-linear fashion. Mitogen-activated protein kinase (MAPK) signal transduction pathways regulate diverse cellular processes ranging from proliferation and differentiation to apoptosis. In mammals, out of five, there are three well characterized subfamilies of MAPKs - ERKs (Extracellular signal-regulated kinases), JNKs (c-Jun N-terminal kinases), and P38 kinases, and their activators, are implicated in human diseases and are targets for drug development. Kinase cascades in MAPK pathways mediate the sensing and processing of stimuli. To understand how cells makes decisions, the dynamic interactions of components of signaling cascades are important rather than just creating static maps. Based on enzyme kinetic reactions, we have developed a mathematical model to analyze the impact of the cross-talks between JNK and P38 kinase cascades. Cross-talks between JNK and P38 kinase cascades influence the activities of P38 kinases. Responses of the signals should be studied for network of kinase cascades by considering cross-talks.

Highlights

All cells receive and respond to signals from their environment, whether they live freely or are part of a tissue
Based on enzyme kinetic reactions, we have developed a mathematical model to analyze the impact of the cross-talks between JNK and P38 kinase cascades
Mitogen-activated protein kinase (MAPK) play an important role in asthma and autoimmunity in humans and are activated by numerous physical and chemical stresses, including hormones, UV

Summary

Background

All cells receive and respond to signals from their environment, whether they live freely or are part of a tissue. MAPK activity is regulated through three-tiered cascades composed of a MAPK, MKK or MAPKK (Mitogen-activated protein kinase kinase) and MEKK or MAPKKK (Mitogenactivated protein kinase kinase kinase) (Figure 1) [1]. Based on the Information’s given in JNK and P38 pathway diagrams deposited in the Science’s STKE(Signal Transduction Knowledge Environment) database [3, 4], we have drawn the diagram (Figure 2) to depict the JNK and P38 Kinase cascades with cross- talks. Mitogen-activated protein kinases (MAPKs) compose a family of protein kinases whose function and regulation have been conserved during evolution from unicellular organisms such as brewers’ yeast to complex organisms including humans, connecting cell-surface receptors to Figure 2: JNK and P38 kinase cascades with cross-talks. The c-Jun N-terminal Kinases consist of three isoforms

Discussion

Methodology: