title: The cyclic nucleotide specificity of eight cAMP-binding proteins in Dictyostelium discoideum is correlated into three groups.
abstract: cAMP is a mediator of inter- and intracellular events in Dictyostelium discoideum and is thought to act through specific receptors. Eight forms of cAMP-binding proteins have been described in this organism: four forms of a cell surface receptor, a cell surface and extracellular phosphodiesterase, an intracellular cAMP-dependent protein kinase (CAK), and a recently identified cAMP-binding protein (CABP1) that is present on the cell surface, in the cytoplasm, and in the nucleus. In this study we have analyzed the cyclic nucleotide specificity of these cAMP-binding proteins using 13 derivatives of cAMP with modifications in the adenine, ribose, and phosphate moiety. The results suggest that the cAMP-binding proteins belong to three groups: (i) four forms of the cell surface receptor, (ii) two forms of an intracellular receptor (CABP1 and CAK), and (iii) cell surface and extracellular phosphodiesterase. cAMP is probably bound to the surface receptors in the anti conformation in a hydrophobic cleft of the receptor with essential interactions at N6H2' and O3'. In contrast, cAMP is probably bound to CAK and CABP1 in the syn conformation with essential interactions at O2', O3', O5', and exocyclic oxygen. Finally, binding of cAMP to phosphodiesterase involves only O3' and exocyclic oxygen. The cyclic nucleotide specificity of cAMP-induced processes in D. discoideum indicates that the cell surface receptors participate in the transduction of the cAMP signal during chemotaxis and cell differentiation. Functions for CABP1 and CAK in these processes are presently elusive.
authors.affiliation: Zoological Laboratory, Leiden University, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Van Ments-Cohen
authors.forename: P J
authors.initials: PJ
authors.lastname: Van Haastert
mesh_terms: D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein; D004023:Dictyostelium / Q000378:metabolism*; D007700:Kinetics; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D009712:Nucleotides, Cyclic; D011953:Receptors, Cyclic AMP