Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
2014-April Volume 9 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
2014-April Volume 9 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells

  • Authors:
    • Ying Wang
    • Yongchang Chen
    • Yueying Li
    • Ting Lan
    • Hai Qian
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
  • Pages: 1444-1452
    |
    Published online on: February 18, 2014
       https://doi.org/10.3892/mmr.2014.1960
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Small GTPase RhoA is a key signaling component regulating cell migration and stress fiber formation. Previous studies have shown that RhoA activity is regulated by protein kinases, such as cAMP‑dependent protein kinase (PKA) and type I cGMP‑dependent protein kinase (PKGI), which phosphorylate the protein. This study was designed to investigate the effect of type II cGMP‑dependent protein kinase (PKGII) on RhoA activity. Cells of the human gastric cancer line AGS were infected with adenoviral constructs bearing the PKGII cDNA in order to increase its endogenous expression, and were treated with 8‑pCPT‑cGMP to activate the PKGII enzyme. A transwell assay was performed to measure the migratory activity of the treated cells, and immunofluorescent microscopy was used to observe the formation of stress fibers. The phosphorylation of RhoA was detected by western blotting, and the activity of RhoA was measured by a pull‑down assay. Co‑immunoprecipitation (co‑IP) was performed to detect binding of PKGII to RhoA. Glutathione S‑transferase (GST)‑fused fragments of RhoA and PKGII were expressed in Escherichia coli and used to investigate the domains required for the binding. The results showed that lysophosphatidic acid (LPA) treatment increased the migration and the formation of stress fibers in AGS cells and that this effect was RhoA‑dependent. An increase in PKGII activity, not only inhibited LPA‑induced migration and stress fiber formation, but also suppressed LPA‑induced activation of RhoA. PKGII caused serine 188 (Ser188) phosphorylation of RhoA, but not the phosphorylation of the mutant RhoA Ser188A, and therefore had no inhibitory effect on the activity of the mutant protein. Co‑IP results showed that there is direct binding of PKGII to RhoA. The GST pull‑down assay showed that the fragment containing RhoA amino acid residues 1‑44 and the N‑terminal fragment of PKGII containing amino acid residues 1‑176 are required for the binding between the two proteins. These results suggested that PKGII inhibits RhoA activity by binding to this small GTPase and causing phosphorylation at its Ser188 site.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Vega FM and Ridley AJ: Rho GTPases in cancer cell biology. FEBS Lett. 582:2093–2101. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Jaffe AB and Hall A: RHO GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 21:247–269. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Etienne-Manneville S and Hall A: Rho GTPases in cell biology. Nature. 420:629–635. 2002. View Article : Google Scholar

4 

Friedl P and Wolf K: Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 3:362–374. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Bos JL, Rehmann H and Wittinghofer A: GEFs and GAPs: critical elements in the control of small G proteins. Cell. 129:865–877. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Forget MA, Desrosiers RR, Gingras D and Beliveau R: Phophorylation states of Cdc42 and RhoA regulate their interactions with Rho GDP dissociation inhibitor and their extraction from biological membranes. Biochem J. 361:243–254. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Lang P, Gesbert F, Delespine-Carmagnat M, Stancou R, Pouchelet M and Bertoglio J: Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. EMBO J. 15:510–519. 1996.PubMed/NCBI

8 

Ellerbroek SM, Wennerberg K and Burridge K: Serine phosphorylation negatively regulates RhoA in vivo. J Biol Chem. 278:19023–19031. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Hofmann F: The biology of cyclic GMP-dependent protein kinases. J Biol Chem. 280:1–4. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Cook AL and Haynes JM: Protein kinase G II-mediated proliferative effects in human cultured prostatic stromal cells. Cell Signal. 16:253–261. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Swartling FJ, Ferletta M, Kastemar M, Weiss WA and Westermark B: Cyclic GMP-dependent protein kinase II inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines. Oncogene. 28:3121–3131. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Wang R, Kwon IK, Thangaraju M, Singh N, Liu K, Jay P, Hofmann F, Ganapathy V and Browning DD: Type 2 cGMP-dependent protein kinase regulates proliferation and differentiation in the colonic mucosa. Am J Physiol Gastrointest Liver Physiol. 303:G209–G219. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Fallahian F, Karami-Tehrani F, Salami S and Aghaei M: Cyclic GMP induced apoptosis via protein kinase G in oestrogen receptor-positive and -negative breast cancer cell lines. FEBS J. 278:3360–3369. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Chen YC, Ren F, Sang JR, Tao Y and Xu WR: Type II cGMP-dependent protein kinase inhibits proliferation of the gastric cancer cell line BGC-823. Mol Med Rep. 3:361–366. 2010.PubMed/NCBI

15 

Wu Y, Chen Y, Qu R, Lan T and Sang J: Type II cGMP-dependent protein kinase inhibits EGF-triggered signal transduction of the MAPK/ERK-mediated pathway in gastric cancer cells. Oncol Rep. 27:553–558. 2012.PubMed/NCBI

16 

Jiang L, Lan T, Chen Y, Sang J, Li Y, Wu M, Tao Y, Wang Y, Qian H and Gu L: PKG II inhibits EGF/EGFR-induced migration of gastric cancer cells. PLoS One. 8:e616742013. View Article : Google Scholar : PubMed/NCBI

17 

Ren F, Gao Q, Tao Y, Sang J, Yang X, Fan S and Chen Y: Impacts of cGMP dependent protein kinase II on gastric cancer cell BGC-823 migration. J Jiangsu Univ (Med Ed). 20:113–116. 2010.

18 

Bian D, Mahanivong C, Yu J, Frisch SM, Pan ZK, Ye RD and Huang S: The G12/13-RhoA signaling pathway contributes to efficient lysophosphatidic acid-stimulated cell migration. Oncogene. 25:2234–2244. 2006.

19 

Kodama Y and Hu CD: An improved bimolecular fluorescence complementation assay with a high signal-to-noise ratio. Biotechniques. 49:793–805. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Kato M, Blanton R, Wang GR, Judson TJ, Abe Y, Myoishi M, Karas RH and Mendelsohn ME: Direct binding and regulation of RhoA protein by cyclic GMP-dependent protein kinase Iα. J Biol Chem. 287:41342–41351. 2012.

21 

Keilbach A, Ruth P and Hofmann F: Detection of cGMP dependent protein kinase isozymes by specific antibodies. Eur J Biochem. 208:467–473. 1992. View Article : Google Scholar : PubMed/NCBI

22 

Deguchi A, Thompson WJ and Weinstein IB: Activation of protein kinase G is sufficient to induce apoptosis and inhibit cell migration in colon cancer cells. Cancer Res. 64:3966–3973. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Hou Y, Gupta N, Schoenlein P, Wong E, Martindale R, Ganapathy V and Browning D: An anti-tumor role for cGMP-dependent protein kinase. Cancer Lett. 240:60–68. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Lohmann SM, Vaandrager AB, Smolenski A, Walter U and De Jonge HR: Distinct and specific functions of cGMP-dependent protein kinases. Trends Biochem Sci. 22:307–312. 1997. View Article : Google Scholar : PubMed/NCBI

25 

Hofmann F, Feil R, Kleppisch T and Schlossmann J: Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol Rev. 86:1–23. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K and Narumiya S: Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 285:895–898. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Yiu G and He Z: Glial inhibition of CNS axon regeneration. Nat Rev Neurosci. 7:617–627. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Caramel J, Quignon F and Delattre O: RhoA-dependent regulation of cell migration by the tumor suppressor hSNF5/INI1. Cancer Res. 68:6154–6161. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Sawada N, Itoh H, Yamashita J, Doi K, Inoue M, Masatsugu K, Fukunaga Y, Sakaguchi S, Sone M, Yamahara K, et al: cGMP-dependent protein kinase phosphorylates and inactivates RhoA. Biochem Biophys Res Commun. 280:798–805. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Sauzeau V, Le Jeune H, Cario-Toumaniantz C, Smolenski A, Lohmann SM, Bertoglio J, Chardin P, Pacaud P and Loirand G: Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem. 275:21722–21729. 2000. View Article : Google Scholar : PubMed/NCBI

31 

Pellegrin S and Mellor H: Actin stress fibres. J Cell Sci. 120:3491–3499. 2007. View Article : Google Scholar

32 

Vaandrager AB, Hogema BM and de Jonge HR: Molecular properties and biological functions of cGMP-dependent protein kinase II. Front Biosci. 10:2150–2164. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Chen Y, Li Y, Lan T and Qian H: Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells. Mol Med Rep 9: 1444-1452, 2014.
APA
Wang, Y., Chen, Y., Li, Y., Lan, T., & Qian, H. (2014). Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells. Molecular Medicine Reports, 9, 1444-1452. https://doi.org/10.3892/mmr.2014.1960
MLA
Wang, Y., Chen, Y., Li, Y., Lan, T., Qian, H."Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells". Molecular Medicine Reports 9.4 (2014): 1444-1452.
Chicago
Wang, Y., Chen, Y., Li, Y., Lan, T., Qian, H."Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells". Molecular Medicine Reports 9, no. 4 (2014): 1444-1452. https://doi.org/10.3892/mmr.2014.1960
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Chen Y, Li Y, Lan T and Qian H: Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells. Mol Med Rep 9: 1444-1452, 2014.
APA
Wang, Y., Chen, Y., Li, Y., Lan, T., & Qian, H. (2014). Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells. Molecular Medicine Reports, 9, 1444-1452. https://doi.org/10.3892/mmr.2014.1960
MLA
Wang, Y., Chen, Y., Li, Y., Lan, T., Qian, H."Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells". Molecular Medicine Reports 9.4 (2014): 1444-1452.
Chicago
Wang, Y., Chen, Y., Li, Y., Lan, T., Qian, H."Type II cGMP‑dependent protein kinase inhibits RhoA activation in gastric cancer cells". Molecular Medicine Reports 9, no. 4 (2014): 1444-1452. https://doi.org/10.3892/mmr.2014.1960
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team