Mitogen-activated Protein Kinases and Mitogen-activated Protein Kinase Phosphatases Mediate the Inhibitory Effects of All-transRetinoic Acid on the Hypertrophic Growth of Cardiomyocytes

Widmann, Christian, Spencer Gibson, Matthew B. Jarpe, and Gary L. Johnson. Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human. Physiol. Rev. 79: 143–180, 1999. — Mitogen-activated protein kinases (MAPK) are serine-threonine protein kinases that are activated by diverse stimuli ranging from cytokines, growth factors, neurotransmitters, hormones, cellular stress, and cell adherence. Mitogen-activated protein kinases are expressed in all eukaryotic cells. The basic assembly of MAPK pathways is a three-component module conserved from yeast to humans. The MAPK module includes three kinases that establish a sequential activation pathway comprising a MAPK kinase kinase (MKKK), MAPK kinase (MKK), and MAPK. Currently, there have been 14 MKKK, 7 MKK, and 12 MAPK identified in mammalian cells. The mammalian MAPK can be subdivided into five families: MAPKerk1/2, MAPKp38, MAPKjnk, MAPKerk3/4, and MAPKerk5. Each MAPK family has distinct biological functions. In Saccharomyces cerevisiae, there are five MAPK pathways involved in mating, cell wall remodelling, nutrient deprivation, and responses to stress stimuli such as osmolarity changes. Component members of the yeast pathways have conserved counterparts in mammalian cells. The number of different MKKK in MAPK modules allows for the diversity of inputs capable of activating MAPK pathways. In this review, we define all known MAPK module kinases from yeast to humans, what is known about their regulation, defined MAPK substrates, and the function of MAPK in cell physiology.

Download Full-text

Following in vitro activation of mitogen-activated protein kinases by mass spectrometry and tryptic peptide analysis: purifying fully activated p38 mitogen-activated protein kinase α

Analytical Biochemistry ◽

10.1016/j.ab.2004.09.039 ◽

2005 ◽

Vol 336 (1) ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Anna E. Szafranska ◽

Xuemei Luo ◽

Kevin N. Dalby

Keyword(s):

Mass Spectrometry ◽

Protein Kinase ◽

Protein Kinases ◽

Tryptic Peptide ◽

Mitogen Activated Protein Kinase ◽

Peptide Analysis ◽

Mitogen Activated Protein Kinases ◽

In Vitro Activation ◽

Mitogen Activated Protein

Download Full-text

Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by the G-protein-coupled receptor agonist phenylephrine in the perfused rat heart

Biochemical Journal ◽

10.1042/bj3320459 ◽

1998 ◽

Vol 332 (2) ◽

pp. 459-465 ◽

Cited By ~ 54

Author(s):

Antigone LAZOU ◽

Peter H. SUGDEN ◽

Angela CLERK

Keyword(s):

Protein Kinase ◽

Protein Kinases ◽

P38 Mapk ◽

Mitogen Activated Protein Kinase ◽

Hypertrophic Growth ◽

Mitogen Activated Protein ◽

Powerful Activator ◽

P38 Mapk Inhibitor ◽

Cellular Stresses ◽

P38 Mapks

We investigated the ability of phenylephrine (PE), an α-adrenergic agonist and promoter of hypertrophic growth in the ventricular myocyte, to activate the three best-characterized mitogen-activated protein kinase (MAPK) subfamilies, namely p38-MAPKs, SAPKs/JNKs (i.e. stress-activated protein kinases/c-Jun N-terminal kinases) and ERKs (extracellularly responsive kinases), in perfused contracting rat hearts. Perfusion of hearts with 100 µM PE caused a rapid (maximal at 10 min) 12-fold activation of two p38-MAPK isoforms, as measured by subsequent phosphorylation of a p38-MAPK substrate, recombinant MAPK-activated protein kinase 2 (MAPKAPK2). This activation coincided with phosphorylation of p38-MAPK. Endogenous MAPKAPK2 was activated 4–5-fold in these perfusions and this was inhibited completely by the p38-MAPK inhibitor, SB203580 (10 µM). Activation of p38-MAPK and MAPKAPK2 was also detected in non-contracting hearts perfused with PE, indicating that the effects were not dependent on the positive inotropic/chronotropic properties of the agonist. Although SAPKs/JNKs were also rapidly activated, the activation (2–3-fold) was less than that of p38-MAPK. The ERKs were activated by perfusion with PE and the activation was at least 50% of that seen with 1 µM PMA, the most powerful activator of the ERKs yet identified in cardiac myocytes. These results indicate that, in addition to the ERKs, two MAPK subfamilies, whose activation is more usually associated with cellular stresses, are activated by the Gq/11-protein-coupled receptor (Gq/11PCR) agonist, PE, in whole hearts. These data indicate that Gq/11PCR agonists activate multiple MAPK signalling pathways in the heart, all of which may contribute to the overall response (e.g. the development of the hypertrophic phenotype).

Download Full-text