G protein-coupled receptors (GPCR) trigger dissociation of GA and GBG heterotrimeric G proteins upon agonist stimulation

G protein-coupled receptors (GPCR) trigger dissociation of Gα and Gβγ heterotrimeric G proteins upon agonist stimulation. Uncoupled heterotrimer subunits elicit signaling cascades through downstream effector proteins. Many of these pathways elicit functional responses through signaling to PLD in multiple ways (). In the canonical pathway, upon agonist stimulation, GTP-Gαq stimulates PLCβ hydrolysis of PI(4,5)P2, producing DAG and IP3 (see excellent reviews by Rhee 2001 on PLC subtype activation, Hubbard and Hepler 2006 for review on Gq family, and Harden review in this issue). IP3 triggers calcium release from the ER, and this coupled with DAG synergistically activates PKCα, which in turn bimodally activates PLD (discussed in section 10.3.4.2). Litosch and colleagues recently showed that this PLCβ signaling is potentiated by PLD-produced PA., Dissociated Gβγ also activates PLCβ, to indirectly activate PLD in a PKC-dependent manner. Additionally, Preninger et al. demonstrated that the Gβγ subunit of the heterotrimer can directly inhibit PLD activity via interactions through the PLD catalytic domain. Gβγ interaction disrupts both basal and Arf-stimulated activity., As illustrated in , levels of PLD activation are intricately titrated in response to specific agonist-mediated or intracellular circumstances.

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Phospholipase D - enzymology, functionality, and chemical modulation. () Paige E. Selvy, et al. Chem Rev. ;111(10):6064-6119. Figure: F9. All organisms Drosophila melanogaster Homo sapiens

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