Multiple, PKA-dependent and PKA-independent, signals are involved in cAMP-induced PRL expression in the eosinophilic cell line Eol-1.
Besides its pivotal role in reproduction, the polypeptide hormone prolactin (PRL) has been attributed an immunomodulatory function. Extrapituitary PRL expression is regulated differently from that in the pituitary, due to the use of an alternative promoter. In leukocytes, cAMP is an important regulator of PRL expression. We report that in the human eosinophilic cell line Eol-1, cAMP-induced PRL expression is partially abrogated by two protein kinase A (PKA) inhibitors (H89, PKI) and by the p38 inhibitor SB203580. Phosphorylation of p38 was PKA-independent and could be stimulated by a methylated cAMP analogue, which specifically activates the exchange factor directly activated by cAMP (EPAC). Furthermore, cAMP induced a PKA-dependent phosphorylation of cAMP-responsive element binding protein (CREB). We postulate that cAMP induces PRL expression via two different signalling pathways: a PKA-dependent pathway leading to the phosphorylation of CREB, and a PKA-independent pathway leading to the phosphorylation of p38.
Gerlo
Sarah
S
Laboratory of Neuroendocrine Immunology, Department of Pharmacology, Free University of Brussels (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium. Sarah.Gerlo@vub.ac.be
Verdood
Peggy
P
Hooghe-Peters
Elisabeth L
EL
Kooijman
Ron
R
D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D004804:Eosinophils / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008894:Milk Proteins / Q000378:metabolism; D010766:Phosphorylation; D011388:Prolactin / Q000096:biosynthesis*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D008894:Milk Proteins; C116122:RAPGEF3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011388:Prolactin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases