Gβγ-mediated activation of protein kinase D exhibits subunit specificity and requires Gβγ-responsive phospholipase Cβ isoforms

Cell Communication and Signaling

Research

Lydia SW Poon¹  Winnie WI Lau¹  Anthony SL Chan¹  Jing Zhu¹  Yung H Wong² 

[1] Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong;Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong;State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong;

关键词: G proteins;    Gα subunits;    Gβγ dimers;    PLCβ;    PKD;   

DOI  :  10.1186/1478-811X-11-22

 received in 2012-11-20, accepted in 2013-03-22,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundProtein kinase D (PKD) constitutes a novel family of serine/threonine protein kinases implicated in fundamental biological activities including cell proliferation, survival, migration, and immune responses. Activation of PKD in these cellular activities has been linked to many extracellular signals acting through antigen receptor engagement, receptor tyrosine kinases, as well as G protein-coupled receptors. In the latter case, it is generally believed that the Gα subunits of the Gq family are highly effective in mediating PKD activation, whereas little is known with regard to the ability of Gβγ dimers and other Gα subunits to stimulate PKD. It has been suggested that the interaction between Gβγ and the PH domain of PKD, or the Gβγ-induced PLCβ/PKC activity is critical for the induction of PKD activation. However, the relative contribution of these two apparently independent events to Gβγ-mediated PKD activation has yet to be addressed.ResultsIn this report, we demonstrate that among various members in the four G protein families, only the Gα subunits of the Gq family effectively activate all the three PKD isoforms (PKD1/2/3), while Gα subunits of other G protein families (Gs, Gi, and G12) are ineffective. Though the Gα subunits of Gi family are unable to stimulate PKD, receptors linked to Gi proteins are capable of triggering PKD activation in cell lines endogenously expressing (HeLa cells and Jurkat T-cells) or exogenously transfected with (HEK293 cells) Gβγ-sensitive PLCβ2/3 isoforms. This indicates that the Gi-mediated PKD activation is dependent on the released Gβγ dimers upon stimulation. Further investigation on individual Gβγ combinations (i.e. Gβ1 with Gγ1–13) revealed that, even if they can stimulate the PLCβ activity in a comparable manner, only those Gβ1γ dimers with γ2, γ3, γ4, γ5, γ7, and γ10 can serve as effective activators of PKD. We also demonstrated that Gi-mediated PKD activation is essential for the SDF-1α-induced chemotaxis on Jurkat T-cells.ConclusionsOur current report illustrates that Gβγ dimers from the Gi proteins may activate PKD in a PLCβ2/3-dependent manner, and the specific identities of Gγ components within Gβγ dimers may determine this stimulatory action.

【 授权许可】

Unknown   
© Lau et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.