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
February-2016 Volume 13 Issue 2

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
February-2016 Volume 13 Issue 2

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 directly inhibits HER2 activation of gastric cancer cells

  • Authors:
    • Miaolin Zhu
    • Xiaoyuan Yao
    • Min Wu
    • Hai Qian
    • Yan Wu
    • Yongchang Chen
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
  • Pages: 1909-1913
    |
    Published online on: December 17, 2015
       https://doi.org/10.3892/mmr.2015.4688
  • 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

Our previous study demonstrated that type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) inhibited epidermal growth factor (EGF)-induced phosphorylation/activation of epidermal growth factor receptor (EGFR). Since human epidermal growth factor receptor 2 (HER2) has a similar molecular structure to EGFR, the present study was designed to investigate whether PKG II also inhibits HER2 activation. The human gastric cancer cell line HGC‑27 was infected with an adenoviral construct encoding cDNA of PKG II (Ad‑PKG II) to increase the expression of PKG II and treated with 8‑(4‑chlorophenylthio)guanosine‑3',5'‑cyclic monophosphate (8‑pCPT‑cGMP) to activate the kinase. Western blotting was performed to detect the tyrosine and serine/threonine phosphorylation of HER2. Co‑immunoprecipitation was performed in order to determine the binding between PKG II and HER2. In addition, a QuikChange Lightning Site‑Directed Mutagenesis kit was used to mutate threonine 686 of HER2 to glutamic acid or alanine. The results demonstrated that EGF treatment increased the tyrosine phosphorylation (activation) of HER2. Increasing the PKG II activity of HGC‑27 cells through infection with Ad‑PKG II and stimulation with 8‑pCPT‑cGMP inhibited the EGF‑induced tyrosine phosphorylation/activation of HER2. PKG II bound directly with HER2 and caused phosphorylation of threonine 686. When threonine 686 of HER2 was mutated to alanine, which could not be phosphorylated by PKG II, the inhibitory effect of PKG II on the activation of HER2 was eradicated. When threonine 686 of HER2 was mutated to glutamic acid, which mimicked the phosphorylation of this site, treatment with EGF had no stimulating effect on tyrosine phosphorylation/activation of the mutant HER2. The results suggested that PKG II inhibits EGF‑induced activation of HER2 through binding with and causing threonine 686 phosphorylation of this oncogenic protein.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Ménard S, Casalini P, Campiglio M, Pupa SM and Tagliabue E: Role of HER2/neu in tumor progression and therapy. Cell Mol Life Sci. 61:2965–2978. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Kim KC, Koh YW, Chang HM, Kim TH, Yook JH, Kim BS, Jang SJ and Park YS: Evaluation of HER2 protein expression in gastric carcinomas: Comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol. 18:2833–2840. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Jørgensen JT: Role of human epidermal growth factor receptor 2 in gastric cancer: Biological and pharmacological aspects. World J Gastroenterol. 20:4526–4535. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Olayioye MA: Update on HER-2 as a target for cancer therapy: Intracellular signaling pathways of ErbB2/HER-2 and family members. Breast Cancer Res. 3:385–389. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Olayioye MA, Graus-Porta D, Beerli RR, Rohrer J, Gay B and Hynes NE: ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner. Mol Cell Biol. 18:5042–5051. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Roy V and Perez EA: Beyond trastuzumab: Small molecule tyrosine kinase inhibitors in HER-2-positive breast cancer. Oncologist. 14:1061–1069. 2009. View Article : Google Scholar : PubMed/NCBI

7 

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.

8 

Lan T, Chen Y, Sang J, Wu Y, Wang Y, Jiang L and Tao Y: Type II cGMP-dependent protein kinase inhibits EGF-induced MAPK/JNK signal transduction in breast cancer cells. Oncol Rep. 27:2039–2044. 2012.PubMed/NCBI

9 

Taniyama K, Ishida K, Toda T, Motoshita J, Kuraoka K, Saito A, Tani Y, Uike T, Teramoto S and Koseki M: Tyrosine1248-phosphorylated HER2 expression and HER2 gene amplification in female invasive ductal carcinomas. Breast Cancer. 15:231–240. 2008. View Article : Google Scholar : PubMed/NCBI

10 

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

11 

Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, Negri E, La Vecchia C and Lunet N: Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015 and incidence by subtype. Eur J Cancer. 50:1330–1344. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Hynes NE and MacDonald G: ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 21:177–184. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Olayioye MA, Neve RM, Lane HA and Hynes NE: The ErbB signaling network: Receptor heterodimerization in development and cancer. Embo J. 19:3159–3167. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Birtwistle MR, Hatakeyama M, Yumoto N, Ogunnaike BA, Hoek JB and Kholodenko BN: Ligand-dependent responses of the ErbB signaling network: Experimental and modeling analyses. Mol Syst Biol. 3:1442007. View Article : Google Scholar : PubMed/NCBI

15 

Gulliford T, Ouyang X and Epstein RJ: Intensification of growth factor receptor signalling by phorbol treatment of ligand-primed cells implies a dimerstabilizing effect of protein kinase C-dependent juxtamembrane domain phosphorylation. Cell Signal. 11:245–252. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Monje PV, Athauda G and Wood PM: Protein kinase A-mediated gating of neuregulin-dependent ErbB2-ErbB3 activation underlies the synergistic action of cAMP on Schwann cell proliferation. J Biol Chem. 283:34087–34100. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Fink BE, Norris D, Mastalerz H, Chen P, Goyal B, Zhao Y, Kim SH, Vite GD, Lee FY, Zhang H, et al: Novel pyrrolo[2,1-f] [1,2,4] triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases. Bioorg Med Chem Lett. 21:781–785. 2011. View Article : Google Scholar

18 

Xia W, Mullin RJ, Keith BR, Liu LH, Ma H, Rusnak DW, Owens G, Alligood KJ and Spector NL: Anti-tumor activity of GW572016: A dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene. 21:6255–6263. 2002. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhu M, Yao X, Wu M, Qian H, Wu Y and Chen Y: Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells. Mol Med Rep 13: 1909-1913, 2016.
APA
Zhu, M., Yao, X., Wu, M., Qian, H., Wu, Y., & Chen, Y. (2016). Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells. Molecular Medicine Reports, 13, 1909-1913. https://doi.org/10.3892/mmr.2015.4688
MLA
Zhu, M., Yao, X., Wu, M., Qian, H., Wu, Y., Chen, Y."Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells". Molecular Medicine Reports 13.2 (2016): 1909-1913.
Chicago
Zhu, M., Yao, X., Wu, M., Qian, H., Wu, Y., Chen, Y."Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells". Molecular Medicine Reports 13, no. 2 (2016): 1909-1913. https://doi.org/10.3892/mmr.2015.4688
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu M, Yao X, Wu M, Qian H, Wu Y and Chen Y: Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells. Mol Med Rep 13: 1909-1913, 2016.
APA
Zhu, M., Yao, X., Wu, M., Qian, H., Wu, Y., & Chen, Y. (2016). Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells. Molecular Medicine Reports, 13, 1909-1913. https://doi.org/10.3892/mmr.2015.4688
MLA
Zhu, M., Yao, X., Wu, M., Qian, H., Wu, Y., Chen, Y."Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells". Molecular Medicine Reports 13.2 (2016): 1909-1913.
Chicago
Zhu, M., Yao, X., Wu, M., Qian, H., Wu, Y., Chen, Y."Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells". Molecular Medicine Reports 13, no. 2 (2016): 1909-1913. https://doi.org/10.3892/mmr.2015.4688
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