A ROLE FOR CAMP-DEPENDENT PROTEIN KINASE-A IN EARLY DICTYOSTELIUM DEVELOPMENT

被引:59
作者
FIRTEL, RA
CHAPMAN, AL
机构
[1] Department of Biology, Center Molecular Genetics, University of California, La Jolla
关键词
cAMP-dependent protein kinase A; Dictyostelium; gene regulation;
D O I
10.1101/gad.4.1.18
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In Dictyostelium, cAMP functions as an extracellular regulatory molecule that controls aggregation, expression of a number of classes of genes, and cellular differentiation by binding to cell-surface receptors that activate intracellular signal transduction pathways. To investigate possible roles for intracellular cAMP we have overexpressed the wild-type-I regulatory subunit (R1) of cAMP-dependent protein C (PKA) in Dictyostelium cells, as well as mutant forms of the subunit that are altered in their ability to bind cAMP. We show that overexpression of a mutated R1, which lacks both cAMP-binding sites and presumably forms a complex with the endogenous Dictyostelium catalytic subunit that cannot be activated by cAMP, results in cells that do not aggregate or express sets of genes that are normally induced in the multicellular stages. Transformations that express the mutant subunit at low levels show no observable phenotype. We show that these cells can respond to pulses of cAMP and activate cAMP receptor/G protein-mediated processes, including the activation of adenylate and guanlyate cyclases and the induction of a class of genes known to be regulated through the receptor-mediated pathways; however, the cells do show an altered pattern of expression of other genes normally active during the preaggregation/interphase and aggregation stages. Of interest is a substantial overexpression of the developmentally regulated PDE mRNA. Cell lines carrying constructs encoding the wild-type subunit or mutant subunits lacking one of the two binding sites show no visual phenotype. The results suggest that PKA-mediated functions, presumably controlled by increases in intracellular cAMP, are essential for Dictyostelium aggregation.
引用
收藏
页码:18 / 28
页数:11
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