A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy (Nat Med, 2009, 15:75-83)

報告日期: 2009/04/21
報告時間: 17:05/17:55
報告學生: 張程翔(英文報告)
講評老師: 蔡美玲


A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy

Kristina Lorenz, Joachim P Schmitt, Eva M Schmitteckert & Martin J Lohse

Nature Medicine 15, 75 - 83 (2009)


Student: 張程翔

Commentator: 蔡美玲 老師 

Time: 2009/4/21/17:05 ~ 17:55

Place: 602



Cardiac hypertrophy, a compensatory response of cardiomyocytes against environmental stress, involves Raf-Mek-Erk pathway. Previous study showed that Gbg proteins mediate Erk signal through binding with Raf. Thus, the authors hypothesized that Gbg affects cardiac hypertrophy through Raf-Mek-Erk pathway. They discovered an unidentified Erk phosphorylation site, Thr188, which is distinct from classical phosphorylation sites, Thr183 and Tyr185. Gbg interacted with Raf, MeK and Erk individually, and subsequently caused Thr188 phosphorylation. The Gbg-induced Thr188 phosphorylation was existed in cardiac hypertrophy and heart failure. The authors found that Gag-coupled receptor was the upstream signal of Thr188 phosphorylation. In addition, receptor tyrosine kinases (RTK) were also proved to trigger Thr188 phosphorylation, suggesting that Thr188 phosphorylation may mediate the cross-talk between RTK and G proteins. Transgenic mice with gain-of-function at Thr188 increased stress-induced cardiac hypertrophy, whereas loss-of-function at Thr188 attenuated. Furthermore, Thr188 phosphorylation mediated nuclear translocation of Erk and phosphorylation of nuclear targets, such as Elk1, known to initiate cardiac hypertrophy. Taken together, the authors discovered and characterized a new phosphorylation site on Erk Thr188, and demonstrated that this phosporylation played a critical role in cardiac hypertrophy.



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