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ROLE OF BIX02188 IN THE STUDY OF ERK5
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Posted On :
Nov-09-2011
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Article Word Count :
461
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Being a potent inhibitor of ERK5 and MEK5, BIX02188 helped in the study of the effects of steady flow of blood. It also helped to prove that ERK5 is very essential for the growth of the neuronal tissues.
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Tumor necrosis factor-alpha stimulates the expression of VCAM1 within the endothelial cells. A steady flow of the fluid inhibits this expression of VCAM1 by blocking the activation of JNK. A steady flow of the fluid (laminar flow) maintains the shear stress at 12 dyn/cm2. This shear stress of the fluid increases the activity of ERK5 or BMK1. This further activates ERK1/2 within the endothelial cells. The activation of JNK induced by TNF is also inhibited by the constant flow. BIX02188 reverses the effects of the steady flow completely. BIX02188 molecule helped in the analysis of pathway initiated by TNF within EC. This also suggests that the TNF mediated pathway moves through MEK5 followed by ERK5. The pathway mediated through MEK1- ERK1/2 does not have any role in the response generated by the steady flow of fluids. Hence the steady flow of blood is atheroprotective in nature [1].
The atheroprotective nature of the steady flow may be due to the increase in the survival of the endothelial cells. The MAPK pathway plays a vital role in stimulating the cell survival. ERK5 alternatively known as BMK1 or Big Mitogen-Activated Protein Kinase1 is stimulated by the shear stress of the fluids. In order to study its role BMK1 was activated by MEK5 within endothelial cells. When growth factor is deprived for more than 24 hours, the activity of caspase-3 is increased by 5.2-fold and the cell gets succumbed to the process of apoptosis. When BMK1 is activated by MEK5 the viability of the cells is increased, this further decreases the rate of apoptosis. MEK5 over expression suppresses the caspase-3 activity. Phosphorylation of the antiapoptotic protein, Bad takes place at the serine residues situated in the positions 112 and 136 due to the activation of BMK1. This suggests that the protective action by the steady flow is due to the phosphorylation of the Bad protein [2].
The differentiation of neurons and their survival is regulated by the ERK5/BMK1 protein. The pathway involving the activation of ERK5 has been less studied when compared to the MAPK pathway which involves ERK1/2. BIX02188 is an inhibitor of MEK5-ERK5 pathway and this helped in the study of the physiological role of ERK5. The C –terminal of ERK5 is unique and codes for nuclear localization signal. This region is made up of two proline rich regions. The catalytic kinase domain is coded by the N-terminal half of the ERK5 [3] [4]. The pathway for the activation of ERK5 starts from GPCRs (G-Protein-Coupled Receptors) and moves through MEKK2,3 and MEK5.
Being a potent inhibitor of ERK5 and MEK5, BIX02188 helped in the study of the effects of steady flow of blood. It also helped to prove that ERK5 is very essential for the growth of the neuronal tissues.
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Article Source :
http://www.articleseen.com/Article_ROLE OF BIX02188 IN THE STUDY OF ERK5_101841.aspx
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Author Resource :
We has established long-term and stable relationships with more than 10,000 customers from pharmaceutical and biotech companies, universities and research institutions. We have high quality inhibitors like MS-275, PD 0332991, pd184352 & more. We have headquarters in both United States and Europe,
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Keywords :
abt-263, Axitinib, bcl-2 inhibitors,
Category :
Health and Fitness
:
Medicine
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