Abstract
Mice with deficiencies in one or more Gq class alpha subunit genes were used to examine the role of the alpha subunit in regulating Ca2+ signaling in pancreatic and submandibular gland cells. Western blot analysis showed that these cells express three of the four Gq class subunits, Galphaq, Galpha11, and Galpha14 but not Galpha15. Surprisingly, all parameters of Ca2+ signaling were identical in cells from wild type and four lines of mutant mice: 1) Galpha11-/-, 2) Galpha11-/-/Galpha14-/-, 3) Galpha14-/-/Galpha15-/-, and 4) Galphaq-/-/Galpha15-/-. These parameters included the Kapp for several Gq class coupled receptors, induction of [Ca2+]i oscillations by weak stimulation, and a biphasic [Ca2+]i response by strong stimulation. Furthermore, Ca2+ release from internal stores and Ca2+ entry were not affected in cells from any of the mutant mice. We conclude that Galphaq, Galpha11, and Galpha14 promiscuously couple several receptors (m3 muscarinic, bombesin, cholecystokinin, and alpha1 adrenergic) to effector proteins that activate both Ca2+ release from internal stores and Ca2+ entry.
Highlights
Heterotrimeric guanine nucleotide-binding proteins (G proteins) couple seven transmembrane domain receptors and effector proteins to regulate the cytosolic concentration of second messengers such as cAMP, cGMP, and [Ca2ϩ]i [1,2,3]
Most effector proteins are regulated by G␣, G␥ contribute to the selectivity of receptor-G protein coupling (4 – 6)
These results suggested that G␣q and G␣11 coupled the same receptor type to stimulate distinct functions in smooth muscle cells
Summary
Heterotrimeric guanine nucleotide-binding proteins (G proteins) couple seven transmembrane domain receptors and effector proteins to regulate the cytosolic concentration of second messengers such as cAMP, cGMP, and [Ca2ϩ]i [1,2,3]. In the present work we used gene knockouts of Gq class ␣ subunits in mice to re-evaluate the specificity of receptor coupling and their subsequent regulation of defined Ca2ϩ transport pathways in pancreatic and submandibular gland cells.
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