Modelling of promiscuous receptor-Gi/Gs-protein coupling and effector response.
A single G-protein-coupled receptor might activate multiple G-protein species. This multiplex coupling ability can be used by tissues to regulate signalling; for the pharmacologist, such multiplex coupling might cause difficulties in the interpretation of experimental data. In this article, we present mathematical models for the activation of two separate G-protein species by a single receptor. Issues addressed concern mutual antagonism between the G proteins and the availability of an already activated receptor for interaction with a new G protein (receptor-G-protein-effector complexing versus free diffusion of G proteins) in addition to receptor-G-protein precoupling at different G-protein and receptor expression levels. The output from the receptor models uses, as readout, a new model for adenylyl cyclase regulation by two allosteric regulators (i.e. G(s) and G(i)).
Kukkonen
J P
JP
Dept of Physiology, Division of Cell Physiology, Uppsala University, BMC,PO Box 572,SE-75123, Uppsala, Sweden. jkukkone@fysiologie.uu.se
Näsman
J
J
Akerman
K E
KE
D000818:Animals; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological
D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs