Activation of MEK-ERK by heregulin-beta1 promotes the development of cardiomyocytes derived from ES cells.
We have previously shown that heregulin-beta1 (HRG-beta1) was involved in the development and survival of cardiomyocytes derived from embryonic stem (ES) cells. This study was conducted to investigate the intracellular signal mechanisms by which HRG-beta1 stimulates cardiogenesis in ES cells. The treatment with ErbB receptor inhibitor decreased the population of cardiomyocytes and transcripts levels of cardiac genes (Nkx2.5, beta-MHC, cTnI, and MLC2a). The phosphorylation of ERK and development of cardiomyocytes by treatment with HRG-beta1 was suppressed upon treatment with MEK1 inhibitor. Furthermore, cardiomyocytes and level of MHC protein were significantly increased by overexpression of wild type MEK1 or constitutive active MEK1, but not dominant negative MEK1. These results suggest that HRG-beta1 promotes the development of cardiomyocytes predominantly by activation of MEK-ERK.
Department of Biology and Institute of Life Science and Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea. hoeskim@snu.ac.kr [corrected]
Hoe Suk
HS
Kim
Jin Won
JW
Cho
Kyoko
K
Hidaka
Takayuki
T
Morisaki
D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology*; D020890:Neuregulin-1 / Q000378:metabolism*; D011799:Quinazolines; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020032:Tyrphostins / Q000494:pharmacology
D020890:Neuregulin-1; D011799:Quinazolines; D020032:Tyrphostins; C087230:heregulin beta1; C101044:RTKI cpd; D020794:Receptor Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases