Phosphorylation by p38 MAPK as an Alternative Pathway for GSK3beta Inactivation

by: Tina M Thornton, Gustavo Pedraza-Alva, Bin Deng, David C Wood, Alexander Aronshtam, James L Clements, Guadalupe Sabio, Roger J Davis, Dwight E Matthews, Bradley Doble, Mercedes Rincon

Science, Vol. 320, No. 5876. (2 May 2008), pp. 667-670.

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Abstract

Glycogen synthase kinase 3 (GSK3) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3 activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3 by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3 substrate -catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3 by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of -catenin. p38 MAPK-mediated phosphorylation of GSK3 occurs primarily in the brain and thymocytes. Activation of -catenin-mediated signaling through GSK3 inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues. 10.1126/science.1156037

@article{citeulike:2746053, abstract = {Glycogen synthase kinase 3 (GSK3) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3 activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3 by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3 substrate -catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3 by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of -catenin. p38 MAPK-mediated phosphorylation of GSK3 occurs primarily in the brain and thymocytes. Activation of -catenin-mediated signaling through GSK3 inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues. 10.1126/science.1156037}, author = {Thornton, Tina M. and Pedraza-Alva, Gustavo and Deng, Bin and Wood, David C. and Aronshtam, Alexander and Clements, James L. and Sabio, Guadalupe and Davis, Roger J. and Matthews, Dwight E. and Doble, Bradley and Rincon, Mercedes }, citeulike-article-id = {2746053}, doi = {http://dx.doi.org/10.1126/science.1156037}, journal = {Science}, keywords = {kinase, signaling}, month = {May}, number = {5876}, pages = {667--670}, posted-at = {2008-05-05 18:18:58}, priority = {2}, title = {Phosphorylation by p38 MAPK as an Alternative Pathway for GSK3{beta} Inactivation}, url = {http://dx.doi.org/10.1126/science.1156037}, volume = {320}, year = {2008} }

RIS record

TY - JOUR ID - citeulike:2746053 L3 - citeulike-article-id:2746053 TI - Phosphorylation by p38 MAPK as an Alternative Pathway for GSK3{beta} Inactivation JF - Science VL - 320 IS - 5876 SP - 667 EP - 670 N2 - Glycogen synthase kinase 3 (GSK3) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3 activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3 by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3 substrate -catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3 by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of -catenin. p38 MAPK-mediated phosphorylation of GSK3 occurs primarily in the brain and thymocytes. Activation of -catenin-mediated signaling through GSK3 inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues. 10.1126/science.1156037 KW - kinase KW - signaling AU - Thornton, Tina AU - Pedraza-Alva, Gustavo AU - Deng, Bin AU - Wood, David AU - Aronshtam, Alexander AU - Clements, James AU - Sabio, Guadalupe AU - Davis, Roger AU - Matthews, Dwight AU - Doble, Bradley AU - Rincon, Mercedes PY - 2008/05/02/ UR - http://dx.doi.org/10.1126/science.1156037 ER -

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