scholarly journals Phosphorylation and activation of mitogen- and stress-activated protein kinase-1 in adult rat cardiac myocytes by G-protein-coupled receptor agonists requires both extracellular-signal-regulated kinase and p38 mitogen-activated protein kinase

2002 ◽  
Vol 365 (3) ◽  
pp. 757-763 ◽  
Author(s):  
Thomais MARKOU ◽  
Antigone LAZOU
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
Cardiac Myocytes ◽  
P38 Mapk ◽  
Mitogen Activated Protein Kinase ◽  
G Protein Coupled Receptor ◽  
Receptor Agonists ◽  
Adult Rat ◽  
G Protein Coupled ◽  
Rat Cardiac Myocytes

G-protein-coupled receptor agonists are powerful stimulators of mitogen-activated protein kinase (MAPK) cascades in cardiac myocytes. However, little is known regarding the physiological activation of enzymes downstream of MAPKs. We examined the activation of mitogen- and stress-activated protein kinase-1 (MSK1), a downstream target of MAPKs, in adult rat cardiac myocytes by phenylephrine and endothelin-1. Both agonists induced the phosphorylation of MSK1 at Thr-581 and Ser-376 but not at Ser-360. Maximal phosphorylation was observed at 10–15min after stimulation and it correlated with increased activity. Maximal activation of MSK1 in adult cardiomyocytes temporally coincided with maximal p38 MAPK activation while activation of the extracellular-signal-regulated kinase (ERK) cascade was more rapid. Phosphorylation and activation of MSK1 was completely inhibited by either PD98059 (ERK1/2 pathway inhibitor) or SB203580 (p38 MAPK inhibitor) alone. These data demonstrate that MSK1 activation in adult rat cardiac myocytes by G-protein-coupled receptor agonists requires the simultaneous activation of both the ERK and p38 MAPK pathways. However, the lack of phosphorylation at Ser-360, an identified phosphorylation site targeted by MAPKs, may indicate that MSK1 is not a direct substrate of ERK1/2 and p38 MAPK in adult rat cardiomyocytes.

scholarly journals The G Protein-coupled Receptor Gpr1 and the Gα Protein Gpa2 Act through the cAMP-Protein Kinase A Pathway to Induce Morphogenesis inCandida albicans

2005 ◽  
Vol 16 (4) ◽  
pp. 1971-1986 ◽  
Author(s):  
Mykola M. Maidan ◽  
Larissa De Rop ◽  
Joke Serneels ◽  
Simone Exler ◽  
Steffen Rupp ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
G Protein ◽  
Mitogen Activated Protein Kinase ◽  
Camp Signaling ◽  
G Protein Coupled Receptor ◽  
Gene Encoding ◽  
Pka Pathway ◽  
G Protein Coupled ◽  
Kinase A

We investigated the role in cell morphogenesis and pathogenicity of the Candida albicans GPR1 gene, encoding the G protein-coupled receptor Gpr1. Deletion of C. albicans GPR1 has only minor effects in liquid hypha-inducing media but results in strong defects in the yeast-to-hypha transition on solid hypha-inducing media. Addition of cAMP, expression of a constitutively active allele of the Gα protein Gpa2 or of the catalytic protein kinase A subunit TPK1 restores the wild-type phenotype of the CaGPR1-deleted strain. Overexpression of HST7, encoding a component of the mitogen-activated protein kinase pathway, does not suppress the defect in filamentation. These results indicate that CaGpr1 functions upstream in the cAMP–protein kinase A (PKA) pathway. We also show that, in the presence of glucose, CaGpr1 is important for amino acid-induced transition from yeast to hyphal cells. Finally, as opposed to previous reports, we show that CaGpa2 acts downstream of CaGpr1 as activator of the cAMP–PKA pathway but that deletion of neither CaGpr1 nor CaGpa2 affects glucose-induced cAMP signaling. In contrast, the latter is abolished in strains lacking CaCdc25 or CaRas1, suggesting that the CaCdc25-CaRas1 rather than the CaGpr1-CaGpa2 module mediates glucose-induced cAMP signaling in C. albicans.

PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation

2005 ◽  
Vol 288 (5) ◽  
pp. H2111-H2117 ◽  
Author(s):  
Mariela Mendez ◽  
Margot C. LaPointe
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
G Protein ◽  
Cardiac Myocytes ◽  
Receptor Activation ◽  
Prostaglandin E ◽  
G Protein Coupled Receptor ◽  
Mapk Activation ◽  
Hypertrophic Growth ◽  
G Protein Coupled

Upon induction of cyclooxygenase-2 (COX-2), neonatal ventricular myocytes (VMs) mainly synthesize prostaglandin E2 (PGE2). The biological effects of PGE2 are mediated through four different G protein-coupled receptor (GPCR) subtypes (EP1–4). We have previously shown that PGE2 stimulates cAMP production and induces hypertrophy of VMs. Because the EP4 receptor is coupled to adenylate cyclase and increases in cAMP, we hypothesized that PGE2 induces hypertrophic growth of cardiac myocytes through a signaling cascade that involves EP4-cAMP and activation of protein kinase A (PKA). To test this, we used primary cultures of VMs and measured [3H]leucine incorporation into total protein. An EP4 antagonist was able to partially block PGE2 induction of protein synthesis and prevent PGE2-dependent increases in cell surface area and activity of the atrial natriuretic factor promoter, which are two other indicators of hypertrophic growth. Surprisingly, a PKA inhibitor had no effect. In other cell types, G protein-coupled receptor activation has been shown to transactivate the epidermal growth factor receptor (EGFR) and result in p42/44 mitogen-activated protein kinase (MAPK) activation and cell growth. Immunoprecipitation of myocyte lysates demonstrated that the EGFR was rapidly phosphorylated by PGE2 in VMs, and the EP4 antagonist blocked this. In addition, the selective EGFR inhibitor AG-1478 completely blocked PGE2-induced protein synthesis. We also found that PGE2 rapidly phosphorylated p42/44 MAPK, which was inhibited by the EP4 antagonist and by AG-1478. Finally, the p42/44 MAPK inhibitor PD-98053 (25 μmol/l) blocked PGE2-induced protein synthesis. Altogether, we believe these are the first data to suggest that PGE2 induces protein synthesis in cardiac myocytes in part via activation of the EP4 receptor and subsequent activation of p42/44 MAPK. Activation of p42/44 MAPK is independent of the common cAMP-PKA pathway and involves EP4-dependent transactivation of EGFR.

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