title: Selective induction of gene expression and second-messenger accumulation in Dictyostelium discoideum by the partial chemotactic antagonist 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate.
abstract: During development of the cellular slime mold Dictyostelium discoideum, cAMP induces chemotaxis and expression of different classes of genes by means of interaction with surface cAMP receptors. We describe a cAMP derivative, 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate (8-CPT-cAMP), which inhibits cAMP-induced chemotaxis at low concentrations but induces chemotaxis at supersaturating concentrations. This compound, moreover, selectively activates expression of aggregative genes but not of postaggregative genes. 8-CPT-cAMP induces normal cGMP and cAMP accumulation but in contrast to cAMP, which increases inositol 1,4,5-trisphosphate levels, 8-CPT-cAMP decreases inositol 1,4,5-trisphosphate levels. The derivative induces reduced activation of guanine nucleotide regulatory proteins, which may cause its defective activation of inositol 1,4,5-trisphosphate production. Our data suggest that disruption of inositolphospholipid signaling impairs chemotaxis and expression of a subclass of cAMP-regulated genes.
authors.affiliation: Department of Biology, University of Leiden, 2311 GP Leiden, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Peters
authors.forename: A A
authors.initials: AA
authors.lastname: Bominaar
authors.forename: B E
authors.initials: BE
authors.lastname: Snaar-Jagalska
authors.forename: R
authors.initials: R
authors.lastname: Brandt
authors.forename: P J
authors.initials: PJ
authors.lastname: Van Haastert
authors.forename: A
authors.initials: A
authors.lastname: Ceccarelli
authors.forename: J G
authors.initials: JG
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Schaap