title: G protein-coupled receptor kinase GRK5 phosphorylates moesin and regulates metastasis in prostate cancer.
abstract: G protein-coupled receptor kinases (GRK) regulate diverse cellular functions ranging from metabolism to growth and locomotion. Here, we report an important contributory role for GRK5 in human prostate cancer. Inhibition of GRK5 kinase activity attenuated the migration and invasion of prostate cancer cells and, concordantly, increased cell attachment and focal adhesion formation. Mass spectrometric analysis of the phosphoproteome revealed the cytoskeletal-membrane attachment protein moesin as a putative GRK5 substrate. GRK5 regulated the subcellular distribution of moesin and colocalized with moesin at the cell periphery. We identified amino acid T66 of moesin as a principal GRK5 phosphorylation site and showed that enforcing the expression of a T66-mutated moesin reduced cell spreading. In a xenograft model of human prostate cancer, GRK5 silencing reduced tumor growth, invasion, and metastasis. Taken together, our results established GRK5 as a key contributor to the growth and metastasis of prostate cancer.
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Prabir Kumar
authors.initials: PK
authors.lastname: Chakraborty
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Coomes
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Rachel
authors.initials: R
authors.lastname: Stupay
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Lauren D
authors.initials: LD
authors.lastname: Lynch
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Tamieka
authors.initials: T
authors.lastname: Atkinson
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Jae I
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Nie
authors.affiliation: Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida ydaaka@ufl.edu.
authors.forename: Yehia
authors.initials: Y
authors.lastname: Daaka
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D022001:Focal Adhesions / Q000473:pathology; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000276:immunology / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D000906:Antibodies; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C071058:moesin; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human