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Molecular and Cellular Pathobiology

G Protein–Coupled Receptor Kinase GRK5 Phosphorylates Moesin and Regulates Metastasis in Prostate Cancer

Prabir Kumar Chakraborty, Yushan Zhang, Alexandra S. Coomes, Wan-Ju Kim, Rachel Stupay, Lauren D. Lynch, Tamieka Atkinson, Jae I. Kim, Zhongzhen Nie and Yehia Daaka
Prabir Kumar Chakraborty
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Yushan Zhang
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Alexandra S. Coomes
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Wan-Ju Kim
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Rachel Stupay
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Lauren D. Lynch
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Tamieka Atkinson
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Jae I. Kim
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Zhongzhen Nie
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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Yehia Daaka
Authors' Affiliation: Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida
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  • For correspondence: ydaaka@ufl.edu
DOI: 10.1158/0008-5472.CAN-13-2708 Published July 2014
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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. Cancer Res; 74(13); 3489–500. ©2014 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received September 19, 2013.
  • Revision received April 9, 2014.
  • Accepted April 14, 2014.
  • ©2014 American Association for Cancer Research.
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Cancer Research: 74 (13)
July 2014
Volume 74, Issue 13
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G Protein–Coupled Receptor Kinase GRK5 Phosphorylates Moesin and Regulates Metastasis in Prostate Cancer
Prabir Kumar Chakraborty, Yushan Zhang, Alexandra S. Coomes, Wan-Ju Kim, Rachel Stupay, Lauren D. Lynch, Tamieka Atkinson, Jae I. Kim, Zhongzhen Nie and Yehia Daaka
Cancer Res July 1 2014 (74) (13) 3489-3500; DOI: 10.1158/0008-5472.CAN-13-2708

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G Protein–Coupled Receptor Kinase GRK5 Phosphorylates Moesin and Regulates Metastasis in Prostate Cancer
Prabir Kumar Chakraborty, Yushan Zhang, Alexandra S. Coomes, Wan-Ju Kim, Rachel Stupay, Lauren D. Lynch, Tamieka Atkinson, Jae I. Kim, Zhongzhen Nie and Yehia Daaka
Cancer Res July 1 2014 (74) (13) 3489-3500; DOI: 10.1158/0008-5472.CAN-13-2708
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