RRC ID 28977
Author Caterina MJ, Milne JL, Devreotes PN.
Title Mutation of the third intracellular loop of the cAMP receptor, cAR1, of Dictyostelium yields mutants impaired in multiple signaling pathways.
Journal J Biol Chem
Abstract Seven-membrane span receptors transduce a wide range of signals across the plasma membrane. One member of this family, the cAMP receptor, cAR1, of Dictyostelium, mediates some responses (e.g. adenylyl cyclase activation, multicellular aggregation) which require G-proteins and others (e.g. Ca2+ influx, loss of ligand binding, cAR1 phosphorylation) which appear to be G-protein-independent. In this study, we randomly mutagenized the NH2-terminal eight amino acids of the third intracellular loop of cAR1 and examined the ability of these mutants to exhibit the three G-protein-independent responses listed above. Most mutants (classes I, II) exhibited wild-type or midly defective responses. Several mutants (class III), however, were severely impaired in all three processes but not in cAMP binding. Furthermore, these mutants failed to couple productively with G-proteins and could not replace cAR1 in a car1- cell. For these reasons, we propose that class III mutations interfere with the formation of an "active" conformation of the receptor.
Volume 269(2)
Pages 1523-32
Published 1994-1-14
PII S0021-9258(17)42288-5
PMID 8288619
MeSH Amino Acid Sequence Animals Base Sequence Biological Transport Calcium / metabolism Cyclic AMP / metabolism DNA Mutational Analysis Dictyostelium GTP-Binding Proteins / physiology Molecular Sequence Data Oligodeoxyribonucleotides / chemistry Phosphorylation Point Mutation Protein Structure, Tertiary Receptors, Cyclic AMP / genetics Receptors, Cyclic AMP / metabolism* Signal Transduction Structure-Activity Relationship
IF 4.238
Times Cited 72
Cellular slime molds S00056 S00152 S00343