ROLE OF BIX02188 IN THE STUDY OF ERK5 Posted On : Nov-09-2011 | seen (481) times | Article Word Count : 461 |
Being a potent inhibitor of ERK5 and MEK5 Riley Ridley Jersey , 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. 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 dyncm2. This shear stress of the fluid increases the activity of ERK5 or BMK1. This further activates ERK12 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- ERK12 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 David Montgomery Jersey , 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 ERK5BMK1 protein. The pathway involving the activation of ERK5 has been less studied when compared to the MAPK pathway which involves ERK12. BIX02188 is an inhibitor of MEK5-ERK5 pathway and this helped in the study of the physiological role of ERK5. The C 鈥搕erminal 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.
Who said that every wish would be heard and answered
~ The Rainbow Connection (sung by Kermit in the Muppets movie)
Yesterday I had a wonderful 'moment? with my daughter. She has just advanced to the next level in her voice lessons. (This is the only lessonclub she is currently involved in, so it is the subject of much conversation.) She was complaining about the ?old songs? she has to sing. She had hoped this next level would bring some ?pop? music.
As a mom would do, I asked her Mitchell Trubisky Jersey , ?How bad can it be?? She proceeded to get her music book. After beautifully belting out ?On Top of Spaghetti,? ?Hello Muddh, Hello Fadduh! Anthony Miller Jersey ,? ?Castle on a Cloud,? and ?Second Hand Rose,? she launched into ?The Rainbow Connection.? I immediately started to clap and stomp my feet Roquan Smith Jersey , looking more like 10 years of age than she does.
?Yes, mother?? She seemed surprised by my excitement.
?I love this song!? I said, quickly joining in. As we sung the chorus above Khalil Mack Jersey , memories began drifting into today. Memories I might not have recalled if it wasn't for this ?old music? in my daughter's voice lessons.
We hit the last part of the song, and it affected me just as it had twenty years ago, when I watched the Muppet movie for the hundredth time.
Have you been half asleep and have you heard voices?
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19.12.2019 08:28
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