Mutation of the third intracellular loop of the cAMP receptor, cAR1, of Dictyostelium yields mutants impaired in multiple signaling pathways

Michael J. Caterina, Jacqueline L.S. Milne, Peter N. Devreotes

Research output: Contribution to journalArticlepeer-review

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 mildly 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.

Original languageEnglish (US)
Pages (from-to)1523-1532
Number of pages10
JournalJournal of Biological Chemistry
Volume269
Issue number2
StatePublished - Jan 14 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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