Phosphorylation pathway of ERK5 is inhibited by BIX02189

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Phosphorylation pathway of ERK5 is inhibited by BIX02189

Posted On : Jan-09-2012 | seen (813) times | Article Word Count : 906 |

ERK5 is an important MAPK family member. It must be in activated form for the proper growth and maintenance of the neuronal cells and tissues. Phosphorylation pathway of ERK5 is inhibited by BIX02189. And this BIX 02189 is an effective key to analyze the function of ERK5 and the pathways activated by it. Molecular size of ERK1/2 is half of the size of ERK5 indeed while the amino terminals of both are almost homologous.

INTRODUCTION

ERK5 is an important MAPK family member. It must be in activated form for the proper growth and maintenance of the neuronal cells and tissues. Phosphorylation pathway of ERK5 is inhibited by BIX02189. And this BIX 02189 is an effective key to analyze the function of ERK5 and the pathways activated by it. Molecular size of ERK1/2 is half of the size of ERK5 indeed while the amino terminals of both are almost homologous. However there is a unique nature of its carboxyl terminal due to having high proline regions and a nuclear localization signal [1].

BIX02189 TARGETS ERK5 SIGNALLING PATHWAY

Cell proliferation, growth or differentiation, and cell death are majorly regulated by MAP Kinases or ERKs. The use of BIX02189 inhibitor made possible to study the signaling pathway leading to ERK5 through G-proteins as BIX02189 is a kinase inhibitor. Activation of transcription of different genes is depended on phosphorylation of ERK5. ERK5 is activated by the autophosphorylation of carboxy terminus. It is further phosphorylated at tyrosine and threonine residues by activated MEK5. The G-protein coupled signaling pathways leading to ERKs are studied by the inhibitor BIX02189 [2]. ERK5 pathway is stimulated by variety of ligands, for instance various growth factors for example NGF, EGF, and stimulants like stress etc. ERK activation is coupled with heterotrimeric G proteins (G13, G12?and Gq?) [1]. Other small proteins like Rac, Rho, Ras and?Cdc42 are not involved in this process. The major pathway among many pathways in activation of ERK5 is signaling pathway of MEKK2/3-MEK5.

Gi/o (?? subunits) causes the down regulation of ERK5 signaling pathway. The actual mechanism controlling this inhibition is the involvement of EGF receptor and its binding affinity for ?? subunits of Gi/o .Tyrosine residues of EGF receptor gets autophosphorylated and inhibited partially in turn stimulating Gi/o , ?? subunits to bind with EGF receptor site. Inhibition of the interaction between tyrosine kinase and MEKK2/3 is mediated by G?? [4].

NEUROTROPHINS STIMULATED BIX02189 FURTHER ACTIVATE THE ERK5

Catecholamines synthesis takes place by the enzyme tyrosine hydroxylase while the control of levels of these catecholamines lies in activation of ERK5. BDNF and NGF like Neutrotrophins are responsible of activating ERK5 by first activating Rap1. Ras is a famous family of proteins. Rap1 also belongs to this family of proteins. Neutrophins activate it and it further activates ERK5 utilizing MEKK2 activation pathway. Thus an essential requirement for the active survival of neuronal tissues is Rap 1 stimulated the pathway of MEKK/MEK5/ERK5. Neuronal tissues stop growing when BIX02189 mediated blockage of MEK5/ERK5 signaling pathway takes place. This compound can also be used in combination of other MAPK inhibitors such as BI6727 and INCB018424.

MEK5 IS INHIBITED BY BIX02189

MEK5 is a kinase by nature and this catalytic activity MEK5 enzyme can be inhibited by BIX02189 like other kinase inhibitors. Its specific action is the ERK5 phosphorylation inside the Hela cells while it does not have any role for ERK1/2 like its phosphorylation or activation. A downstream effect in ERK5/ MEK5 signaling pathway has observed caused by MEF2C. And this is due to the suppression of transcriptional activity induced by BIX02189 [5].

CONCLUSION

Specific activity of ERK5 in the cells is studied by the scientists due to the recently discovered inhibitor of ERK5 and MEK5 named BIX02189. This inhibitor played a key role in discovering the significant effects of ERK5. In short BIX02189 inhibitor helped the scientists in studying that how the tyrosine hydrolase enzymes levels are maintained by the activation and deactivation of ERK5. This BIX02189 inhibitor proved to be a gateway in analyzing that how ERK5/ MEK5pathway affect in the cells physiologically.

REFERENCES

1. Obara Y, Nakahata N. The signaling pathway leading to extracellular signal-regulated kinase 5 (ERK5) activation via G-proteins and ERK5-dependent neurotrophic effects. Mol Pharmacol 2010 Jan; 77(1):10-6.

2. Morimoto H, Kondoh K, et al. Activation of a C-terminal Transcriptional Activation Domain of ERK5 by Autophosphorylation. The Journal of Biological Chemistry 2007 Dec 7; 282: 35449-35456.

3. Kato Y, Tapping RI, et al. Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature 1998 Oct 15; 395(6703):713-6.

4. Obara Y, Okano Y, et al. Betagamma subunits of G(i/o) suppress EGF-induced ERK5 phosphorylation, whereas ERK1/2 phosphorylation is enhanced. Cell Signal 2008 Jul; 20(7):1275-83.

5. Tatake RJ, Neill MM, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun 2008 Dec 5; 377(1):120-5.

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<h1>Phosphorylation pathway of ERK5 is inhibited by BIX02189</h1> Author: <a href='http://www.articleseen.com/profile_Dr.Rabia.aspx'>Dr.Rabia</a> INTRODUCTION

BIX02189 TARGETS ERK5 SIGNALLING PATHWAY

Cell proliferation, growth or differentiation, and cell death are majorly regulated by MAP Kinases or ERKs. The use of BIX02189 inhibitor made possible to study the signaling pathway leading to ERK5 through G-proteins as BIX02189 is a kinase inhibitor. Activation of transcription of different genes is depended on phosphorylation of ERK5. ERK5 is activated by the autophosphorylation of carboxy terminus. It is further phosphorylated at tyrosine and threonine residues by activated MEK5. The G-protein coupled signaling pathways leading to ERKs are studied by the inhibitor BIX02189 [2]. ERK5 pathway is stimulated by variety of ligands, for instance various growth factors for example NGF, EGF, and stimulants like stress etc. ERK activation is coupled with heterotrimeric G proteins (G13, G12?and Gq?) [1]. Other small proteins like Rac, Rho, Ras and?Cdc42 are not involved in this process. The major pathway among many pathways in activation of ERK5 is signaling pathway of MEKK2/3-MEK5.

Gi/o (?? subunits) causes the down regulation of ERK5 signaling pathway. The actual mechanism controlling this inhibition is the involvement of EGF receptor and its binding affinity for ?? subunits of Gi/o .Tyrosine residues of EGF receptor gets autophosphorylated and inhibited partially in turn stimulating Gi/o ,  ?? subunits to bind with EGF receptor site. Inhibition of the interaction between tyrosine kinase and MEKK2/3 is mediated by G?? [4].

NEUROTROPHINS STIMULATED BIX02189 FURTHER ACTIVATE THE ERK5

Catecholamines synthesis takes place by the enzyme tyrosine hydroxylase while the control of levels of these catecholamines lies in activation of ERK5. BDNF and NGF like Neutrotrophins are responsible of activating ERK5 by first activating Rap1. Ras is a famous family of proteins. Rap1 also belongs to this family of proteins. Neutrophins activate it and it further activates ERK5 utilizing MEKK2 activation pathway. Thus an essential requirement for the active survival of neuronal tissues is Rap 1 stimulated the pathway of MEKK/MEK5/ERK5. Neuronal tissues stop growing when BIX02189 mediated blockage of MEK5/ERK5 signaling pathway takes place. This compound can also be used in combination of other MAPK inhibitors such as BI6727 and INCB018424.

MEK5 IS INHIBITED BY BIX02189

MEK5 is a kinase by nature and this catalytic activity MEK5 enzyme can be inhibited by BIX02189 like other kinase inhibitors. Its specific action is the ERK5 phosphorylation inside the Hela cells while it does not have any role for ERK1/2 like its phosphorylation or activation. A downstream effect in ERK5/ MEK5 signaling pathway has observed caused by MEF2C. And this is due to the suppression of transcriptional activity induced by BIX02189 [5].

CONCLUSION

Specific activity of ERK5 in the cells is studied by the scientists due to the recently discovered inhibitor of ERK5 and MEK5 named BIX02189. This inhibitor played a key role in discovering the significant effects of ERK5. In short BIX02189 inhibitor helped the scientists in studying that how the tyrosine hydrolase enzymes levels are maintained by the activation and deactivation of ERK5. This BIX02189 inhibitor proved to be a gateway in analyzing that how ERK5/ MEK5pathway affect in the cells physiologically.

REFERENCES

1. Obara Y, Nakahata N. The signaling pathway leading to extracellular signal-regulated kinase 5 (ERK5) activation via G-proteins and ERK5-dependent neurotrophic effects. Mol Pharmacol 2010 Jan; 77(1):10-6.

2. Morimoto H, Kondoh K, et al. Activation of a C-terminal Transcriptional Activation Domain of ERK5 by Autophosphorylation. The Journal of Biological Chemistry 2007 Dec 7; 282: 35449-35456.

3. Kato Y, Tapping RI, et al. Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature 1998 Oct 15; 395(6703):713-6.

4. Obara Y, Okano Y, et al. Betagamma subunits of G(i/o) suppress EGF-induced ERK5 phosphorylation, whereas ERK1/2 phosphorylation is enhanced. Cell Signal 2008 Jul; 20(7):1275-83.

5. Tatake RJ, Neill MM, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun 2008 Dec 5; 377(1):120-5.

Related Posts:
BIX 02188: A STRONG INHIBITOR OF STEADY FLOW
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INTRODUCTION ERK5 is a member of the MAPK family of proteins. Its activation is required the regular maintenance and growth of neuronal tissues. BIX 02189 ...
    BIX 02188: A STRONG INHIBITOR OF STEADY FLOW

INTRODUCTION A steady blood flow is the only case of prevention of atherosclerosis. A shear stress can cause the prevention of hardening of blood vessels. ...
    BIX02188: HELPS IN THE STUDY OF PHYSIOLOGICAL ROLE OF ERK5

INTRODUCTION During atherosclerosis, the walls of the arteries get thickened and hardened due to the deposition of fats towards the inner side of the walls. ...About the Author: We pays great attention to the purity, stability and activity of the products like <a rel="nofollow" href="http://www.selleckchem.com/products/ABT-869.html">ABT-869</a>, <a rel="nofollow" href="http://www.selleckchem.com/products/Y-27632.html">Y-27632</a>, <a rel="nofollow" href="http://www.selleckchem.com/products/ABT-869.html">Linifanib</a> & more. Article Source: <a href='http://www.articleseen.com/Article_Phosphorylation-pathway-of-ERK5-is-inhibited-by-BIX02189_131113.aspx'> http://www.articleseen.com/Article_Phosphorylation pathway of ERK5 is inhibited by BIX02189_131113.aspx</a>

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