Figure 9
A schematic diagram for the Gβγ -mediated PKD activation. PLCβ2/3 serves as important intermediates for the Gβγ-mediated PKD activation, in which intracellular scaffold proteins may facilitate or determine the formation of functional complexes among these signaling players. Scaffold proteins (e.g. NHERFs and others) may form functional complexes with specific PLCβ isoforms and PKDs, only those complexes containing PLCβ2/3 will enable Gβγ dimers to be recruited and interact with PKDs. The Gβγ/PLCβ2/3-induced DAG production leads to confirmation changes of PKDs as well as PKC-mediated phosphorylation on the kinases. As demonstrated in the current report, enhanced Gβγ-induced PLCβ2/3 stimulation alone does not guarantee a successful PKD activation, it is possible that only specific Gβγ dimers (e.g. Gβ1γ2) are compatible with the PH domain of PKDs for productive conformation changes, which result in functional activation of PKDs. Such activation mechanism is not feasible for PLCβ1 which is Gβγ-insensitive.