Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215 - PubMed (original) (raw)

Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215

Ratna K Vadlamudi et al. FEBS Lett. 2003.

Free article

Abstract

To elucidate the molecular mechanisms by which human epidermal growth factor receptor/heregulin (HER2/HRG) influence the migratory potential of breast cancer cells, we have used phospho-specific antibodies against c-Src kinase and focal adhesion kinase (FAK). This study establishes that HER2/HRG signaling selectively upregulates Tyr phosphorylation of c-Src at Tyr-215 located within the SH2 domain, increases c-Src kinase activity and selectively upregulates Tyr phosphorylation of FAK at Tyr-861. HER2-overexpressing tumors showed increased levels of c-Src phosphorylation at Tyr-215. These findings suggest that HER2/HRG influence metastasis of breast cancer cells through a novel signaling pathway involving phosphorylation of FAK tyrosine 861 via activation of c-Src tyrosine 215.

PubMed Disclaimer

Similar articles

• Differential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2.
  Vadlamudi RK, Adam L, Nguyen D, Santos M, Kumar R. Vadlamudi RK, et al. J Cell Physiol. 2002 Feb;190(2):189-99. doi: 10.1002/jcp.10054. J Cell Physiol. 2002. PMID: 11807823
• Csk homologous kinase associates with RAFTK/Pyk2 in breast cancer cells and negatively regulates its activation and breast cancer cell migration.
  McShan GD, Zagozdzon R, Park SY, Zrihan-Licht S, Fu Y, Avraham S, Avraham H. McShan GD, et al. Int J Oncol. 2002 Jul;21(1):197-205. Int J Oncol. 2002. PMID: 12063569
• RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion.
  Zrihan-Licht S, Fu Y, Settleman J, Schinkmann K, Shaw L, Keydar I, Avraham S, Avraham H. Zrihan-Licht S, et al. Oncogene. 2000 Mar 2;19(10):1318-28. doi: 10.1038/sj.onc.1203422. Oncogene. 2000. PMID: 10713673
• Protein kinases in human breast cancer.
  Cance WG, Liu ET. Cance WG, et al. Breast Cancer Res Treat. 1995 Jul;35(1):105-14. doi: 10.1007/BF00694751. Breast Cancer Res Treat. 1995. PMID: 7612897 Review.
• Signal transduction: clamping down on Src activity.
  Mayer BJ. Mayer BJ. Curr Biol. 1997 May 1;7(5):R295-8. doi: 10.1016/s0960-9822(06)00141-2. Curr Biol. 1997. PMID: 9115388 Review.

Cited by

• Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma.
  Yang Z, Liu H, Song Y, Gao N, Gao P, Hui Y, Li Y, Fan T. Yang Z, et al. Int J Mol Med. 2024 Sep;54(3):77. doi: 10.3892/ijmm.2024.5401. Epub 2024 Jul 12. Int J Mol Med. 2024. PMID: 38994756 Free PMC article.
• Inhibiting ERK5 overcomes breast cancer resistance to anti-HER2 therapy by targeting the G1/S cell cycle transition.
  Zhang J, Pearson AJ, Sabherwal N, Telfer BA, Ali N, Kan K, Xu Q, Zhang W, Chen F, Li S, Wang J, Gray NS, Risa-Ebrí B, Finegan KG, Cross MJ, Giurisato E, Whitmarsh AJ, Tournier C. Zhang J, et al. Cancer Res Commun. 2022 Mar 10;2(3):131-145. doi: 10.1158/2767-9764.CRC-21-0089. Cancer Res Commun. 2022. PMID: 36466034 Free PMC article.
• Asporin Interacts With HER2 to Promote Thyroid Cancer Metastasis via the MAPK/EMT Signaling Pathway.
  Zhan S, Wang T, Li J, Zhu H, Ge W, Li J. Zhan S, et al. Front Oncol. 2022 May 2;12:762180. doi: 10.3389/fonc.2022.762180. eCollection 2022. Front Oncol. 2022. PMID: 35600399 Free PMC article.
• Prognostic impact of body mass index (BMI) in HER2+ breast cancer treated with anti-HER2 therapies: from preclinical rationale to clinical implications.
  Ligorio F, Zambelli L, Fucà G, Lobefaro R, Santamaria M, Zattarin E, de Braud F, Vernieri C. Ligorio F, et al. Ther Adv Med Oncol. 2022 Mar 8;14:17588359221079123. doi: 10.1177/17588359221079123. eCollection 2022. Ther Adv Med Oncol. 2022. PMID: 35281350 Free PMC article. Review.
• Galectin-3 Mediates Thrombin-Induced Vascular Smooth Muscle Cell Migration.
  Tian L, Huang CK, Ding F, Zhang R. Tian L, et al. Front Cardiovasc Med. 2021 Oct 20;8:686200. doi: 10.3389/fcvm.2021.686200. eCollection 2021. Front Cardiovasc Med. 2021. PMID: 34746246 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations

• Molecular Biology Databases

  • GlyGen glycoinformatics resource
  • PhosphoSitePlus

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal
  • SciCrunch