Identification of a region at the N-terminus of phospholipase C-beta 3 that interacts with G protein beta gamma subunits

Barr, A.J., Ali, H., Haribabu, B., Snyderman, R. and Smrcka, A.V. 2000. Identification of a region at the N-terminus of phospholipase C-beta 3 that interacts with G protein beta gamma subunits. Biochemistry. 39 (7), pp. 1800-1806.

TitleIdentification of a region at the N-terminus of phospholipase C-beta 3 that interacts with G protein beta gamma subunits
AuthorsBarr, A.J., Ali, H., Haribabu, B., Snyderman, R. and Smrcka, A.V.
Abstract

Members of the phospholipase C-β (PLC-β) family of proteins are activated either by Gα or Gβγ subunits of heterotrimeric G proteins. To define specific regions of PLC-β3 that are involved in binding and activation by Gβγ, a series of fragments of PLC-β3 as glutathione-S-transferase (GST) fusion proteins were produced. A fragment encompassing the N-terminal pleckstrin homology (PH) domain and downstream sequence (GST-N) bound to G protein β1γ2 in an in vitro binding assay, and binding was inhibited by G protein α subunit, Gαi1. This PLC-β3 fragment also inhibited Gβγ-stimulated PLC-β activity in a reconstitution system, while having no significant effect on Gαq-stimulated PLC-β3 activity. The N-terminal Gβγ binding region was delineated further to the first 180 amino acids, and the sequence Asn150−Ser180, just distal to the PH domain, was found to be required for the interaction. Mutation of basic residues 154Arg, 155Lys, 159Lys, and 161Lys to Glu within this region reduced Gβγ binding affinity and specifically reduced the EC50 for Gβγ-dependent activation of the mutant enzyme 3-fold. Basal activity and Gαq-dependent activation of the enzyme were unaffected by the mutations. While these basic residues may not directly mediate the interaction with Gβγ, the data provide evidence for an N-terminal Gβγ binding region of PLC-β3 that is involved in activation of the enzyme.

JournalBiochemistry
Journal citation39 (7), pp. 1800-1806
ISSN0006-2960
Year2000
PublisherAmerican Chemical Society
Digital Object Identifier (DOI)doi:10.1021/bi992021f
Publication dates
Published2000

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