Antagonistic effects of signal transduction by intracellular and extracellular cAMP on gene regulation in Dictyostelium.
In Dictyostelium, cAMP plays a role as an intracellular second messenger and in addition, as an extracellular first messenger. Both functions are thought to be tightly linked because adenylyl cyclase is coupled via G-proteins to the cell surface cAMP receptor cAR 1. Using the discoidin I gene family as a molecular marker for the first stages of development, we show here that induction of transcription requires the G-protein subunit alpha 2 and thus an as yet unidentified surface receptor, CRAC (cytosolic regulator of adenylyl cyclase), and PKA. Induction can be conferred by an increase in intracellular cAMP. In contrast, transcriptional down-regulation occurs by stimulation of cAR 1 with extracellular cAMP and a subsequent, G-protein-independent Ca2+ influx. In a G alpha 2 gene disruption mutant, discoidin I expression can be efficiently modulated by analogues simulating intracellular cAMP (discoidin induction) and extracellular cAMP (discoidin down-regulation). We thus demonstrate possible antagonistic functions of intra- and extracellular cAMP.
Endl
I
I
Max-Planck-Institut f. Biochemie, Martinsried, Germany.
Konzok
A
A
Nellen
W
W
D000818:Animals; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000070821:Discoidins; D015536:Down-Regulation; D005656:Fungal Proteins / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D037102:Lectins; D008954:Models, Biological; D015800:Protozoan Proteins; D015398:Signal Transduction; D014158:Transcription, Genetic
D000070821:Discoidins; D005656:Fungal Proteins; D037102:Lectins; D015800:Protozoan Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D002118:Calcium