Association of activated Gαq to the tumor suppressor Fhit is enhanced by phospholipase Cβ

BMC Cancer

Research Article

Hao Zuo¹  Yung H. Wong² 

[1] Division of Life Sciences, and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China;Present address: Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, 75390, Dallas, TX, USA;Division of Life Sciences, and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China;State Key Laboratory of Molecular Neuroscience, and the Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong;

关键词: Fhit;    G protein;    Phospholipase Cβ;    Tumor suppression;   

DOI  :  10.1186/s12885-015-1802-z

 received in 2015-07-28, accepted in 2015-10-16,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundG proteins are known to modulate various growth signals and are implicated in the regulation of tumorigenesis. The tumor suppressor Fhit is a newly identified interaction partner of Gq proteins that typically stimulate the phospholipase C pathway. Activated Gαq subunits have been shown to interact directly with Fhit, up-regulate Fhit expression and enhance its suppressive effect on cell growth and migration. Other signaling molecules may be involved in modulating Gαq/Fhit interaction.MethodsTo test the relationship of PLCβ with the interaction between Gαq and Fhit, co-immunoprecipication assay was performed on HEK293 cells co-transfected with different combinations of Flag-Fhit, Gα16, Gα16QL, pcDNA3 vector, and PLCβ isoforms. Possible associations of Fhit with other effectors of Gαq were also demonstrated by co-immunoprecipitation. The regions of Gαq for Fhit interaction and PLCβ stimulation were further evaluated by inositol phosphates accumulation assay using a series of Gα16/z chimeras with discrete regions of Gα16 replaced by those of Gαz.ResultsPLCβ1, 2 and 3 interacted with Fhit regardless of the expression of Gαq. Expression of PLCβ increased the affinities of Fhit for both wild-type and activated Gαq. Swapping of the Fhit-interacting α2-β4 region of Gαq with Gαi eliminated the association of Gαq with Fhit without affecting the ability of the mutant to stimulate PLCβ. Other effectors of Gαq including RGS2 and p63RhoGEF were unable to interact with Fhit.ConclusionsPLCβ may participate in the regulation of Fhit by Gq in a unique way. PLCβ interacts with Fhit and increases the interaction between Gαq and Fhit. The Gαq/PLCβ/Fhit complex formation points to a novel signaling pathway that may negatively regulate tumor cell growth.

【 授权许可】

CC BY   
© Zuo and Wong. 2015