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-Secretase Cleavage and Nuclear Localization of ErbB-4 Receptor Tyrosine Kinase
Chang-Yuan Ni,1M. Paul Murphy,3Todd E. Golde,3Graham Carpenter12*
ErbB-4 is a transmembrane receptor tyrosine kinase that regulates
cell proliferation and differentiation. After binding ofits ligand
heregulin (HRG) or activation of protein kinase C (PKC)by
12-O-tetradecanoylphorbol-13-acetate (TPA), the
ErbB-4 ectodomainis cleaved by a metalloprotease. We now report a
subsequent cleavageby -secretase that releases the ErbB-4
intracellular domain fromthe membrane and facilitates its
translocation to the nucleus.-Secretase cleavage was prevented by
chemical inhibitors or adominant negative presenilin. Inhibition of
-secretase also preventedgrowth inhibition by HRG. -Secretase
cleavage of ErbB-4 may representanother mechanism for receptor
tyrosine kinase-mediated signaling.
1 Department of Biochemistry,
2 Department of Medicine, Vanderbilt University
School of Medicine, Nashville, TN 37232, USA.
3 Department of Neuroscience and Pharmacology, Mayo
Clinic Jacksonville, Jacksonville, FL 32224, USA.
*
To whom correspondence should be addressed. E-mail:
graham.carpenter{at}mcmail.vanderbilt.edu
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ErbB4 Expression in Neural Progenitor Cells (ST14A) Is Necessary to Mediate Neuregulin-1{beta}1-induced Migration.
G. Gambarotta, D. Garzotto, E. Destro, B. Mautino, C. Giampietro, S. Cutrupi, C. Dati, E. Cattaneo, A. Fasolo, and I. Perroteau (2004)
J. Biol. Chem.
279, 48808-48816
|Abstract »|Full Text »|PDF »
The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone.
C. C. Williams, J. G. Allison, G. A. Vidal, M. E. Burow, B. S. Beckman, L. Marrero, and F. E. Jones (2004)
J. Cell Biol.
167, 469-478
|Abstract »|Full Text »|PDF »
ErbB Transmembrane Tyrosine Kinase Receptors Are Expressed by Sensory and Motor Neurons Projecting into Sciatic Nerve.
R. J. Pearson Jr. and S. L. Carroll (2004)
J. Histochem. Cytochem.
52, 1299-1311
|Abstract »|Full Text »|PDF »
Presenilins and {gamma}-Secretase Inhibitors Affect Intracellular Trafficking and Cell Surface Localization of the {gamma}-Secretase Complex Components.
H. Wang, W.-j. Luo, Y.-w. Zhang, Y.-M. Li, G. Thinakaran, P. Greengard, and H. Xu (2004)
J. Biol. Chem.
279, 40560-40566
|Abstract »|Full Text »|PDF »
The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor.
R. C. von Rotz, B. M. Kohli, J. Bosset, M. Meier, T. Suzuki, R. M. Nitsch, and U. Konietzko (2004)
J. Cell Sci.
117, 4435-4448
|Abstract »|Full Text »|PDF »
Purification and Identification of Protein-Tyrosine Kinase-binding Proteins Using Synthetic Phosphopeptides as Affinity Reagents.
K. Wilhelmsen, J. Copp, G. Glenn, R. C. Hoffman, P. Tucker, and P. van der Geer (2004)
Mol. Cell. Proteomics
3, 887-895
|Abstract »|Full Text »|PDF »
Patterns of Chromosomal Alterations in Breast Ductal Carcinoma In situ.
E. S. Hwang, S. DeVries, K. L. Chew, D. H. Moore II, K. Kerlikowske, A. Thor, B.-M. Ljung, and F. M. Waldman (2004)
Clin. Cancer Res.
10, 5160-5167
|Abstract »|Full Text »|PDF »
Notch Oncoproteins Depend on {gamma}-Secretase/Presenilin Activity for Processing and Function.
I. Das, C. Craig, Y. Funahashi, K.-M. Jung, T.-W. Kim, R. Byers, A. P. Weng, J. L. Kutok, J. C. Aster, and J. Kitajewski (2004)
J. Biol. Chem.
279, 30771-30780
|Abstract »|Full Text »|PDF »
Monoubiquitination and endocytosis direct {gamma}-secretase cleavage of activated Notch receptor.
N. Gupta-Rossi, E. Six, O. LeBail, F. Logeat, P. Chastagner, A. Olry, A. Israel, and C. Brou (2004)
J. Cell Biol.
166, 73-83
|Abstract »|Full Text »|PDF »
Presenilin 1 in migration and morphogenesis in the central nervous system.
A. Louvi, S. S. Sisodia, and E. A. Grove (2004)
Development
131, 3093-3105
|Abstract »|Full Text »|PDF »
Coordinated Metabolism of Alcadein and Amyloid {beta}-Protein Precursor Regulates FE65-dependent Gene Transactivation.
Y. Araki, N. Miyagi, N. Kato, T. Yoshida, S. Wada, M. Nishimura, H. Komano, T. Yamamoto, B. De Strooper, K. Yamamoto, et al. (2004)
J. Biol. Chem.
279, 24343-24354
|Abstract »|Full Text »|PDF »
FE65 Constitutes the Functional Link between the Low-Density Lipoprotein Receptor-Related Protein and the Amyloid Precursor Protein.
C. U. Pietrzik, I.-S. Yoon, S. Jaeger, T. Busse, S. Weggen, and E. H. Koo (2004)
J. Neurosci.
24, 4259-4265
|Abstract »|Full Text »|PDF »
-Secretase Cleavage and Nuclear Localization of ErbB-4 Receptor Tyrosine Kinase
-secretase that releases the ErbB-4
intracellular domain from the membrane and facilitates its
translocation to the nucleus. 
