Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Biol. Chem. 277 (21): 18736-18743

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteolytic Processing of Low Density Lipoprotein Receptor-related Protein Mediates Regulated Release of Its Intracellular Domain*

Petra MayDagger , Y. Krishna Reddy§, and Joachim HerzDagger

From the Departments of Dagger  Molecular Genetics and § Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390

The low density lipoprotein (LDL) receptor-related protein (LRP) is a multifunctional cell surface receptor that interacts through its cytoplasmic tail with adaptor and scaffold proteins that participate in cellular signaling. Its extracellular domain, like that of the signaling receptor Notch and of amyloid precursor protein (APP), is proteolytically processed at multiple positions. This similarity led us to investigate whether LRP, like APP and Notch, might also be cleaved at a third, intramembranous or cytoplasmic site, resulting in the release of its intracellular domain. Using independent experimental approaches we demonstrate that the cytoplasmic domain is released by a gamma -secretase-like activity and that this event is modulated by protein kinase C. Furthermore, cytoplasmic adaptor proteins that bind to the LRP tail affect the subcellular localization of the free intracellular domain and may regulate putative signaling functions. Finally, we show that the degradation of the free tail fragment is mediated by the proteasome. These findings suggest a novel role for the intracellular domain of LRP that may involve the subcellular translocation of preassembled signaling complexes from the plasma membrane.

* This work was supported in part by National Institutes of Health Grants HL20948, HL63762, and NS43408, the Deutsche Forschungsgemeinschaft (to P. M.), by the Alzheimer Association, and by the Perot Family Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

An Established Investigator of the American Heart Association and Parke Davis and recipient of a Wolfgang-Paul Award from the Humboldt Foundation. To whom correspondence should be addressed: Dept. of Molecular Genetics, University of Texas Southwestern, 5323 Harry Hines Blvd., Dallas, TX 75390-9046. Tel.: 214-648-5633; Fax: 214-648-8804; E-mail:

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

ApoER2 processing by presenilin-1 modulates reelin expression.
V. Balmaceda, I. Cuchillo-Ibanez, L. Pujadas, M.-S. Garcia-Ayllon, C. A. Saura, J. Nimpf, E. Soriano, and J. Saez-Valero (2014)
FASEB J 28, 1543-1554
   Abstract »    Full Text »    PDF »
Self-renewal and Differentiation of Muscle Satellite Cells Are Regulated by the Fas-associated Death Domain.
W. Cheng, L. Wang, B. Yang, R. Zhang, C. Yao, L. He, Z. Liu, P. Du, K. Hammache, J. Wen, et al. (2014)
J. Biol. Chem. 289, 5040-5050
   Abstract »    Full Text »    PDF »
Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Modulates N-Methyl-D-aspartate (NMDA) Receptor-dependent Intracellular Signaling and NMDA-induced Regulation of Postsynaptic Protein Complexes.
C. Nakajima, A. Kulik, M. Frotscher, J. Herz, M. Schafer, H. H. Bock, and P. May (2013)
J. Biol. Chem. 288, 21909-21923
   Abstract »    Full Text »    PDF »
Abnormal cross-talk between mutant presenilin 1 (I143T, G384A) and glycosphingolipid biosynthesis.
T. Mutoh, N. Kawamura, Y. Hirabayashi, S. Shima, T. Miyashita, S. Ito, K. Asakura, W. Araki, E. Cazzaniga, E. Muto, et al. (2012)
FASEB J 26, 3065-3074
   Abstract »    Full Text »    PDF »
Substrate Sequence Influences {gamma}-Secretase Modulator Activity, Role of the Transmembrane Domain of the Amyloid Precursor Protein.
S. A. Sagi, C. B. Lessard, K. D. Winden, H. Maruyama, J. C. Koo, S. Weggen, T. L. Kukar, T. E. Golde, and E. H. Koo (2011)
J. Biol. Chem. 286, 39794-39803
   Abstract »    Full Text »    PDF »
Regulation of Notch1 signaling by the APP intracellular domain facilitates degradation of the Notch1 intracellular domain and RBP-Jk.
M.-Y. Kim, J.-S. Mo, E.-J. Ann, J.-H. Yoon, J. Jung, Y.-H. Choi, S.-M. Kim, H.-Y. Kim, J.-S. Ahn, H. Kim, et al. (2011)
J. Cell Sci. 124, 1831-1843
   Abstract »    Full Text »    PDF »
A disintegrin and metalloprotease 10 activity sheds the ectodomain of the amyloid precursor-like protein 2 and regulates protein expression in proximal tubule cells.
R. Cong, Y. Li, and D. Biemesderfer (2011)
Am J Physiol Cell Physiol 300, C1366-C1374
   Abstract »    Full Text »    PDF »
Regulated Intramembrane Proteolysis: Signaling Pathways and Biological Functions.
M. Lal and M. Caplan (2011)
Physiology 26, 34-44
   Abstract »    Full Text »    PDF »
Pro-cathepsin D interacts with the extracellular domain of the {beta} chain of LRP1 and promotes LRP1-dependent fibroblast outgrowth.
M. Beaujouin, C. Prebois, D. Derocq, V. Laurent-Matha, O. Masson, S. Pattingre, P. Coopman, N. Bettache, J. Grossfield, R. E. Hollingsworth, et al. (2010)
J. Cell Sci. 123, 3336-3346
   Abstract »    Full Text »    PDF »
Stability elements in the LRP6 cytoplasmic tail confer efficient signalling upon DIX-dependent polymerization.
C. Metcalfe, C. Mendoza-Topaz, J. Mieszczanek, and M. Bienz (2010)
J. Cell Sci. 123, 1588-1599
   Abstract »    Full Text »    PDF »
Amyloid precursor family proteins are expressed by thymic and lymph node stromal cells but are not required for lymphocyte development.
K. Laky, W. Annaert, and B. J. Fowlkes (2009)
Int. Immunol. 21, 1163-1174
   Abstract »    Full Text »    PDF »
Nontraditional Signaling Mechanisms of Lipoprotein Receptors.
G. W. Rebeck (2009)
Science Signaling 2, pe28
   Abstract »    Full Text »    PDF »
MT1-MMP promotes vascular smooth muscle dedifferentiation through LRP1 processing.
K. Lehti, N. F. Rose, S. Valavaara, S. J. Weiss, and J. Keski-Oja (2009)
J. Cell Sci. 122, 126-135
   Abstract »    Full Text »    PDF »
{gamma}-Secretase Limits the Inflammatory Response Through the Processing of LRP1.
K. Zurhove, C. Nakajima, J. Herz, H. H. Bock, and P. May (2008)
Science Signaling 1, ra15
   Abstract »    Full Text »    PDF »
Valproic acid inhibits A{beta} production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models.
H. Qing, G. He, P. T. T. Ly, C. J. Fox, M. Staufenbiel, F. Cai, Z. Zhang, S. Wei, X. Sun, C.-H. Chen, et al. (2008)
J. Exp. Med. 205, 2781-2789
   Abstract »    Full Text »    PDF »
LDL Receptor-Related Protein 1: Unique Tissue-Specific Functions Revealed by Selective Gene Knockout Studies.
A. P. Lillis, L. B. Van Duyn, J. E. Murphy-Ullrich, and D. K. Strickland (2008)
Physiol Rev 88, 887-918
   Abstract »    Full Text »    PDF »
Low-density lipoprotein receptor-related protein promotes amyloid precursor protein trafficking to lipid rafts in the endocytic pathway.
I.-S. Yoon, E. Chen, T. Busse, E. Repetto, M. K. Lakshmana, E. H. Koo, and D. E. Kang (2007)
FASEB J 21, 2742-2752
   Abstract »    Full Text »    PDF »
Nephroblastoma Overexpressed (Nov) Inhibits Osteoblastogenesis and Causes Osteopenia.
S. Rydziel, L. Stadmeyer, S. Zanotti, D. Durant, A. Smerdel-Ramoya, and E. Canalis (2007)
J. Biol. Chem. 282, 19762-19772
   Abstract »    Full Text »    PDF »
Amyloid Precursor Protein and Presenilin1 Interact with the Adaptor GRB2 and Modulate ERK 1,2 Signaling.
M. Nizzari, V. Venezia, E. Repetto, V. Caorsi, R. Magrassi, M. C. Gagliani, P. Carlo, T. Florio, G. Schettini, C. Tacchetti, et al. (2007)
J. Biol. Chem. 282, 13833-13844
   Abstract »    Full Text »    PDF »
Tissue-type plasminogen activator-mediated shedding of astrocytic low-density lipoprotein receptor-related protein increases the permeability of the neurovascular unit.
R. Polavarapu, M. C. Gongora, H. Yi, S. Ranganthan, D. A. Lawrence, D. Strickland, and M. Yepes (2007)
Blood 109, 3270-3278
   Abstract »    Full Text »    PDF »
{gamma}-Secretase-mediated Release of the Low Density Lipoprotein Receptor-related Protein 1B Intracellular Domain Suppresses Anchorage-independent Growth of Neuroglioma Cells.
C.-X. Liu, S. Ranganathan, S. Robinson, and D. K. Strickland (2007)
J. Biol. Chem. 282, 7504-7511
   Abstract »    Full Text »    PDF »
SorLA Signaling by Regulated Intramembrane Proteolysis.
C. Bohm, N. M. Seibel, B. Henkel, H. Steiner, C. Haass, and W. Hampe (2006)
J. Biol. Chem. 281, 14547-14553
   Abstract »    Full Text »    PDF »
Regulation of the Composition of the Extracellular Matrix by Low Density Lipoprotein Receptor-related Protein-1: ACTIVITIES BASED ON REGULATION OF mRNA EXPRESSION.
A. Gaultier, A. M. Salicioni, S. Arandjelovic, and S. L. Gonias (2006)
J. Biol. Chem. 281, 7332-7340
   Abstract »    Full Text »    PDF »
Loss of core fucosylation of low-density lipoprotein receptor-related protein-1 impairs its function, leading to the upregulation of serum levels of insulin-like growth factor-binding protein 3 in fut8-/- mice..
S. H. Lee, M. Takahashi, K. Honke, E. Miyoshi, D. Osumi, H. Sakiyama, A. Ekuni, X. Wang, S. Inoue, J. Gu, et al. (2006)
J. Biochem. 139, 391-398
   Abstract »    Full Text »    PDF »
The Low Density Lipoprotein Receptor-related Protein 6 Interacts with Glycogen Synthase Kinase 3 and Attenuates Activity.
K. Mi, P. J. Dolan, and G. V. W. Johnson (2006)
J. Biol. Chem. 281, 4787-4794
   Abstract »    Full Text »    PDF »
Mutant Lrp1 Knock-In Mice Generated by Recombinase-Mediated Cassette Exchange Reveal Differential Importance of the NPXY Motifs in the Intracellular Domain of LRP1 for Normal Fetal Development.
A. J. M. Roebroek, S. Reekmans, A. Lauwers, N. Feyaerts, L. Smeijers, and D. Hartmann (2006)
Mol. Cell. Biol. 26, 605-616
   Abstract »    Full Text »    PDF »
Presenilin 1 Deficiency Alters the Activity of Voltage-Gated Ca2+ Channels in Cultured Cortical Neurons.
D. G. Cook, X. Li, S. D. Cherry, and A. R. Cantrell (2005)
J Neurophysiol 94, 4421-4429
   Abstract »    Full Text »    PDF »
F-Spondin Interaction with the Apolipoprotein E Receptor ApoEr2 Affects Processing of Amyloid Precursor Protein.
H.-S. Hoe, D. Wessner, U. Beffert, A. G. Becker, Y. Matsuoka, and G. W. Rebeck (2005)
Mol. Cell. Biol. 25, 9259-9268
   Abstract »    Full Text »    PDF »
{gamma}-Secretase Is a Functional Component of Phagosomes.
I. Jutras, A. Laplante, J. Boulais, S. Brunet, G. Thinakaran, and M. Desjardins (2005)
J. Biol. Chem. 280, 36310-36317
   Abstract »    Full Text »    PDF »
Activation of the Notch pathway in Down syndrome: cross-talk of Notch and APP.
D. F. Fischer, R. van Dijk, J. A. Sluijs, S. M. Nair, M. Racchi, C. N. Levelt, F. W. van Leeuwen, and E. M. Hol (2005)
FASEB J 19, 1451-1458
   Abstract »    Full Text »    PDF »
Low Density Lipoprotein Receptor-related Protein (LRP) Interacts with Presenilin 1 and Is a Competitive Substrate of the Amyloid Precursor Protein (APP) for {gamma}-Secretase.
A. Lleo, E. Waldron, C. A. F. von Arnim, L. Herl, M. M. Tangredi, I. D. Peltan, D. K. Strickland, E. H. Koo, B. T. Hyman, C. U. Pietrzik, et al. (2005)
J. Biol. Chem. 280, 27303-27309
   Abstract »    Full Text »    PDF »
Conditional Inactivation of Presenilin 1 Prevents Amyloid Accumulation and Temporarily Rescues Contextual and Spatial Working Memory Impairments in Amyloid Precursor Protein Transgenic Mice.
C. A. Saura, G. Chen, S. Malkani, S.-Y. Choi, R. H. Takahashi, D. Zhang, G. K. Gouras, A. Kirkwood, R. G. M. Morris, and J. Shen (2005)
J. Neurosci. 25, 6755-6764
   Abstract »    Full Text »    PDF »
Presenilin/{gamma}-Secretase-mediated Cleavage of the Voltage-gated Sodium Channel {beta}2-Subunit Regulates Cell Adhesion and Migration.
D. Y. Kim, L. A. M. Ingano, B. W. Carey, W. H. Pettingell, and D. M. Kovacs (2005)
J. Biol. Chem. 280, 23251-23261
   Abstract »    Full Text »    PDF »
NEPH2 Is Located at the Glomerular Slit Diaphragm, Interacts with Nephrin and Is Cleaved from Podocytes by Metalloproteinases.
P. Gerke, L. Sellin, O. Kretz, D. Petraschka, H. Zentgraf, T. Benzing, and G. Walz (2005)
J. Am. Soc. Nephrol. 16, 1693-1702
   Abstract »    Full Text »    PDF »
CD147 is a regulatory subunit of the {gamma}-secretase complex in Alzheimer's disease amyloid {beta}-peptide production.
S. Zhou, H. Zhou, P. J. Walian, and B. K. Jap (2005)
PNAS 102, 7499-7504
   Abstract »    Full Text »    PDF »
Sequences from the Low Density Lipoprotein Receptor-related Protein (LRP) Cytoplasmic Domain Enhance Amyloid {beta} Protein Production via the {beta}-Secretase Pathway without Altering Amyloid Precursor Protein/LRP Nuclear Signaling.
I.-S. Yoon, C. U. Pietrzik, D. E. Kang, and E. H. Koo (2005)
J. Biol. Chem. 280, 20140-20147
   Abstract »    Full Text »    PDF »
Growth Hormone Receptor Is a Target for Presenilin-dependent {gamma}-Secretase Cleavage.
J. W. Cowan, X. Wang, R. Guan, K. He, J. Jiang, G. Baumann, R. A. Black, M. S. Wolfe, and S. J. Frank (2005)
J. Biol. Chem. 280, 19331-19342
   Abstract »    Full Text »    PDF »
The Low Density Lipoprotein Receptor-related Protein (LRP) Is a Novel {beta}-Secretase (BACE1) Substrate.
C. A. F. von Arnim, A. Kinoshita, I. D. Peltan, M. M. Tangredi, L. Herl, B. M. Lee, R. Spoelgen, T. T. Hshieh, S. Ranganathan, F. D. Battey, et al. (2005)
J. Biol. Chem. 280, 17777-17785
   Abstract »    Full Text »    PDF »
A Novel Mechanism of Thyroid Hormone-dependent Negative Regulation by Thyroid Hormone Receptor, Nuclear Receptor Corepressor (NCoR), and GAGA-binding Factor on the Rat CD44 Promoter.
S.-W. Kim, S.-C. Ho, S.-J. Hong, K. M. Kim, E. C. So, M. Christoffolete, and J. W. Harney (2005)
J. Biol. Chem. 280, 14545-14555
   Abstract »    Full Text »    PDF »
Fatty acids increase presenilin-1 levels and {gamma}-secretase activity in PSwt-1 cells.
Y. Liu, L. Yang, K. Conde-Knape, D. Beher, M. S. Shearman, and N. S. Shachter (2004)
J. Lipid Res. 45, 2368-2376
   Abstract »    Full Text »    PDF »
Neuronal LRP1 Functionally Associates with Postsynaptic Proteins and Is Required for Normal Motor Function in Mice.
P. May, A. Rohlmann, H. H. Bock, K. Zurhove, J. D. Marth, E. D. Schomburg, J. L. Noebels, U. Beffert, J. D. Sweatt, E. J. Weeber, et al. (2004)
Mol. Cell. Biol. 24, 8872-8883
   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 »
Z. Zou, B. Chung, T. Nguyen, S. Mentone, B. Thomson, and D. Biemesderfer (2004)
J. Biol. Chem. 279, 34302-34310
   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 »
A phosphorylated, carboxy-terminal fragment of {beta}-amyloid precursor protein localizes to the splicing factor compartment.
Z. Muresan and V. Muresan (2004)
Hum. Mol. Genet. 13, 475-488
   Abstract »    Full Text »    PDF »
Phorbol 12-Myristate 13-Acetate-Induced Release of the Colony-Stimulating Factor 1 Receptor Cytoplasmic Domain into the Cytosol Involves Two Separate Cleavage Events.
K. Wilhelmsen and P. van der Geer (2004)
Mol. Cell. Biol. 24, 454-464
   Abstract »    Full Text »    PDF »
Inhibition of Receptor-mediated Endocytosis Demonstrates Generation of Amyloid {beta}-Protein at the Cell Surface.
J. H. Chyung and D. J. Selkoe (2003)
J. Biol. Chem. 278, 51035-51043
   Abstract »    Full Text »    PDF »
Syndecan 3 Intramembrane Proteolysis Is Presenilin/{gamma}-Secretase-dependent and Modulates Cytosolic Signaling.
J. G. Schulz, W. Annaert, J. Vandekerckhove, P. Zimmermann, B. De Strooper, and G. David (2003)
J. Biol. Chem. 278, 48651-48657
   Abstract »    Full Text »    PDF »
Presenilins Mutated at Asp-257 or Asp-385 Restore Pen-2 Expression and Nicastrin Glycosylation but Remain Catalytically Inactive in the Absence of Wild Type Presenilin.
O. Nyabi, M. Bentahir, K. Horre, A. Herreman, N. Gottardi-Littell, C. Van Broeckhoven, P. Merchiers, K. Spittaels, W. Annaert, and B. De Strooper (2003)
J. Biol. Chem. 278, 43430-43436
   Abstract »    Full Text »    PDF »
The Intracellular Domain of the Low Density Lipoprotein Receptor-related Protein Modulates Transactivation Mediated by Amyloid Precursor Protein and Fe65.
A. Kinoshita, T. Shah, M. M. Tangredi, D. K. Strickland, and B. T. Hyman (2003)
J. Biol. Chem. 278, 41182-41188
   Abstract »    Full Text »    PDF »
Q.-C. Cheng, O. Tikhomirov, W. Zhou, and G. Carpenter (2003)
J. Biol. Chem. 278, 38421-38427
   Abstract »    Full Text »    PDF »
Differential Glycosylation Regulates Processing of Lipoprotein Receptors by {gamma}-Secretase.
P. May, H. H. Bock, J. Nimpf, and J. Herz (2003)
J. Biol. Chem. 278, 37386-37392
   Abstract »    Full Text »    PDF »
Presenilin-dependent "{gamma}-Secretase" Processing of Deleted in Colorectal Cancer (DCC).
Y. Taniguchi, S.-H. Kim, and S. S. Sisodia (2003)
J. Biol. Chem. 278, 30425-30428
   Abstract »    Full Text »    PDF »
A{beta}42-lowering Nonsteroidal Anti-inflammatory Drugs Preserve Intramembrane Cleavage of the Amyloid Precursor Protein (APP) and ErbB-4 Receptor and Signaling through the APP Intracellular Domain.
S. Weggen, J. L. Eriksen, S. A. Sagi, C. U. Pietrzik, Todd. E. Golde, and E. H. Koo (2003)
J. Biol. Chem. 278, 30748-30754
   Abstract »    Full Text »    PDF »
Intramembrane proteolysis by presenilin and presenilin-like proteases.
W. Xia and M. S. Wolfe (2003)
J. Cell Sci. 116, 2839-2844
   Abstract »    Full Text »    PDF »
The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and {gamma}-secretase.
E. Six, D. Ndiaye, Y. Laabi, C. Brou, N. Gupta-Rossi, A. Israel, and F. Logeat (2003)
PNAS 100, 7638-7643
   Abstract »    Full Text »    PDF »
Amyloid Precursor Protein Associates with a Nicastrin-Dependent Docking Site on the Presenilin 1-{gamma}-Secretase Complex in Cells Demonstrated by Fluorescence Lifetime Imaging.
O. Berezovska, P. Ramdya, J. Skoch, M. S. Wolfe, B. J. Bacskai, and B. T. Hyman (2003)
J. Neurosci. 23, 4560-4566
   Abstract »    Full Text »    PDF »
gamma -Secretase Cleavage Site Specificity Differs for Intracellular and Secretory Amyloid beta.
H. S. Grimm, D. Beher, S. F. Lichtenthaler, M. S. Shearman, K. Beyreuther, and T. Hartmann (2003)
J. Biol. Chem. 278, 13077-13085
   Abstract »    Full Text »    PDF »
Integration of Endocytosis and Signal Transduction by Lipoprotein Receptors.
P. May, H. H. Bock, and J. Herz (2003)
Sci. STKE 2003, pe12
   Abstract »    Full Text »    PDF »
{gamma}-Secretase--Intramembrane Protease with a Complex.
M. S. Wolfe (2003)
Sci. Aging Knowl. Environ. 2003, pe7-7
   Abstract »    Full Text »
Physiologic and Pathologic Events Mediated by Intramembranous and Juxtamembranous Proteolysis.
T. E. Golde and C. B. Eckman (2003)
Sci. STKE 2003, re4
   Abstract »    Full Text »    PDF »
The Notch Ligands, Delta1 and Jagged2, Are Substrates for Presenilin-dependent "gamma -Secretase" Cleavage.
T. Ikeuchi and S. S. Sisodia (2003)
J. Biol. Chem. 278, 7751-7754
   Abstract »    Full Text »    PDF »
Nectin-1alpha , an Immunoglobulin-like Receptor Involved in the Formation of Synapses, Is a Substrate for Presenilin/gamma -Secretase-like Cleavage.
D. Y. Kim, L. A. M. Ingano, and D. M. Kovacs (2002)
J. Biol. Chem. 277, 49976-49981
   Abstract »    Full Text »    PDF »
Presenilin-dependent Intramembrane Proteolysis of CD44 Leads to the Liberation of Its Intracellular Domain and the Secretion of an Abeta -like Peptide.
S. Lammich, M. Okochi, M. Takeda, C. Kaether, A. Capell, A.-K. Zimmer, D. Edbauer, J. Walter, H. Steiner, and C. Haass (2002)
J. Biol. Chem. 277, 44754-44759
   Abstract »    Full Text »    PDF »
Processing of beta -Amyloid Precursor-like Protein-1 and -2 by gamma -Secretase Regulates Transcription.
M. H. Scheinfeld, E. Ghersi, K. Laky, B. J. Fowlkes, and L. D'Adamio (2002)
J. Biol. Chem. 277, 44195-44201
   Abstract »    Full Text »    PDF »
The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in APP processing.
C. U. Pietrzik, T. Busse, D. E. Merriam, S. Weggen, and E. H. Koo (2002)
EMBO J. 21, 5691-5700
   Abstract »    Full Text »    PDF »
Evidence of Functional Modulation of the MEKK/JNK/cJun Signaling Cascade by the Low Density Lipoprotein Receptor-related Protein (LRP).
C. Lutz, J. Nimpf, M. Jenny, K. Boecklinger, C. Enzinger, G. Utermann, G. Baier-Bitterlich, and G. Baier (2002)
J. Biol. Chem. 277, 43143-43151
   Abstract »    Full Text »    PDF »
Presenilins mediate a dual intramembranous {gamma}-secretase cleavage of Notch-1.
M. Okochi, H. Steiner, A. Fukumori, H. Tanii, T. Tomita, T. Tanaka, T. Iwatsubo, T. Kudo, M. Takeda, and C. Haass (2002)
EMBO J. 21, 5408-5416
   Abstract »    Full Text »    PDF »
Presenilin-1 affects trafficking and processing of {beta}APP and is targeted in a complex with nicastrin to the plasma membrane.
C. Kaether, S. Lammich, D. Edbauer, M. Ertl, J. Rietdorf, A. Capell, H. Steiner, and C. Haass (2002)
J. Cell Biol. 158, 551-561
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882