Molecular Biology of the Cell Call for Nominations: MBC Editor-in-Chief

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print July 12, 2006
Mol. Biol. Cell 10.1091/mbc.E06-02-0101

A more recent version of this article appeared on September 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E06-02-0101v1
17/9/4118    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Muraoka-Cook, R. S.
Right arrow Articles by Earp, H. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Muraoka-Cook, R. S.
Right arrow Articles by Earp, H. S., III

Submitted on February 6, 2006
Revised on June 13, 2006
Accepted on July 5, 2006

The Intracellular Domain of ErbB4 Induces Differentiation of Mammary Epithelial Cells

Rebecca S. Muraoka-Cook,*{dagger} Melissa Sandahl,* Carty Husted,* Debra Hunter,* Leah Miraglia,* Shu-mang Feng,* Klaus Elenius,{ddagger} and H. Shelton Earp III*{sect}||

*Lineberger Comprehensive Cancer Center and Departments of {dagger}Genetics, {sect}Medicine, and ||Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; {ddagger}Medicity Research Laboratory, Departments of Medical Biochemistry and Molecular Biology and Oncology, University of Turku, FI-20520, Turku, Finland

Monitoring Editor: Carl-Henrik Heldin

Differentiation of mammary epithelium in vivo requires signaling through prolactin and ErbB4/HER4-dependent mechanisms; how these pathways intersect is unknown. We show herein that HC11 mouse mammary cells undergo ErbB4-dependent lactational differentiation. Prolactin and the ErbB4 ligand HB-EGF each induced STAT5A activation, expression of lactogenic differentiation markers, and lumen formation in three-dimensional Matrigel cultures in HC11 cells. ErbB4 undergoes ligand-dependent transmembrane domain cleavage at Val-675, releasing a soluble 80 kDa intracellular domain (s80HER4) that localizes to nuclei; the physiological relevance of s80HER4 is unknown. A HER4V675A mutant abolishing transmembrane cleavage impaired STAT5A activity, lactogenic gene expression, and lumen formation. Kinase-dead HER4KD was neither cleaved nor able to induce differentiation of HC11 cells. Without treating HC11 cells with prolactin or HB-EGF, s80HER4 (expressed from a cDNA construct) localized to the nucleus, activated STAT5A, and induced three-dimensional lumen formation. Nuclear localization of exogenous s80HER4 required intact kinase activity of s80HER4, as did activation of STAT5A. In contrast, nuclear localization of s80HER4 and STAT5A activation did not require the 16-amino acid region of the ErbB4 intracellular domain specific to the Cyt-1 isoform of ErbB4, and absent in the Cyt-2 isoform. These results suggest that s80HER4 formation contributes to ErbB4-dependent differentiation of mammary epithelial cells.

Address correspondence to: H. Shelton Earp (hse{at}med.unc.edu)




This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
R. S. Muraoka-Cook, M. Sandahl, D. Hunter, L. Miraglia, and H. S. Earp III
Prolactin and ErbB4/HER4 Signaling Interact via Janus Kinase 2 to Induce Mammary Epithelial Cell Gene Expression Differentiation
Mol. Endocrinol., October 1, 2008; 22(10): 2307 - 2321.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Naresh, A. D. Thor, S. M. Edgerton, K. C. Torkko, R. Kumar, and F. E. Jones
The HER4/4ICD Estrogen Receptor Coactivator and BH3-Only Protein Is an Effector of Tamoxifen-Induced Apoptosis
Cancer Res., August 1, 2008; 68(15): 6387 - 6395.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
F. Zeng, M.-Z. Zhang, A. B. Singh, R. Zent, and R. C. Harris
ErbB4 Isoforms Selectively Regulate Growth Factor induced Madin-Darby Canine Kidney Cell Tubulogenesis
Mol. Biol. Cell, November 1, 2007; 18(11): 4446 - 4456.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S.-M. Feng, C. I. Sartor, D. Hunter, H. Zhou, X. Yang, L. S. Caskey, R. Dy, R. S. Muraoka-Cook, and H. S. Earp III
The HER4 Cytoplasmic Domain, But Not Its C Terminus, Inhibits Mammary Cell Proliferation
Mol. Endocrinol., August 1, 2007; 21(8): 1861 - 1876.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. E. Strunk, C. Husted, L. C. Miraglia, M. Sandahl, W. A. Rearick, D. M. Hunter, H. S. Earp III, and R. S. Muraoka-Cook
HER4 D-Box Sequences Regulate Mitotic Progression and Degradation of the Nuclear HER4 Cleavage Product s80HER4
Cancer Res., July 15, 2007; 67(14): 6582 - 6590.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2006 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.