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The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1.

Standard

The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1. / Kalus, Ina; Schnegelsberg, Birthe; Seidah, Nabil G; Kleene, Ralf; Schachner, Melitta.

in: J BIOL CHEM, Jahrgang 278, Nr. 12, 12, 2003, S. 10381-10388.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kalus, I, Schnegelsberg, B, Seidah, NG, Kleene, R & Schachner, M 2003, 'The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1.', J BIOL CHEM, Jg. 278, Nr. 12, 12, S. 10381-10388. <http://www.ncbi.nlm.nih.gov/pubmed/12529374?dopt=Citation>

APA

Kalus, I., Schnegelsberg, B., Seidah, N. G., Kleene, R., & Schachner, M. (2003). The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1. J BIOL CHEM, 278(12), 10381-10388. [12]. http://www.ncbi.nlm.nih.gov/pubmed/12529374?dopt=Citation

Vancouver

Kalus I, Schnegelsberg B, Seidah NG, Kleene R, Schachner M. The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1. J BIOL CHEM. 2003;278(12):10381-10388. 12.

Bibtex

@article{92eeb663fb6c41f797c9097a501be15f,
title = "The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1.",
abstract = "The transmembrane and multidomain neural adhesion molecule L1 plays important functional roles in the developing and adult nervous system. L1 is proteolytically processed at two distinct sites within the extracellular domain, leading to the generation of different fragments. In this report, we present evidence that the proprotein convertase PC5A is the protease that cleaves L1 in the third fibronectin type III domain, whereas the proprotein convertases furin, PC1, PC2, PACE4, and PC7 are not effective in cleaving L1. Analysis of mutations revealed Arg(845) to be the site of cleavage generating the N-terminal 140-kDa fragment. This fragment was present in the hippocampus, which expresses PC5A, but was not detectable in the cerebellum, which does not express PC5A. The 140-kDa L1 fragment was found to be tightly associated with the full-length 200-kDa L1 molecule. The complex dissociated from the membrane upon cleavage by a protease acting at a more membrane-proximal site of full-length L1. This proteolytic cleavage was inhibited by the metalloprotease inhibitor GM 6001 and enhanced by a calmodulin inhibitor. L1-dependent neurite outgrowth of cerebellar neurons was inhibited by GM 6001, suggesting that proteolytic processing of L1 by a metalloprotease is involved in neurite outgrowth.",
keywords = "Animals, Mice, Mice, Inbred C57BL, Amino Acid Sequence, Molecular Sequence Data, Amino Acid Motifs, Tumor Cells, Cultured, Dimerization, Serine Endopeptidases/*physiology, Cerebellum/metabolism, Calmodulin/antagonists & inhibitors, Fibronectins/metabolism, Hippocampus/metabolism, Metalloendopeptidases/*physiology, Neural Cell Adhesion Molecule L1/chemistry/*metabolism, Neurites/physiology, Proprotein Convertase 5, Animals, Mice, Mice, Inbred C57BL, Amino Acid Sequence, Molecular Sequence Data, Amino Acid Motifs, Tumor Cells, Cultured, Dimerization, Serine Endopeptidases/*physiology, Cerebellum/metabolism, Calmodulin/antagonists & inhibitors, Fibronectins/metabolism, Hippocampus/metabolism, Metalloendopeptidases/*physiology, Neural Cell Adhesion Molecule L1/chemistry/*metabolism, Neurites/physiology, Proprotein Convertase 5",
author = "Ina Kalus and Birthe Schnegelsberg and Seidah, {Nabil G} and Ralf Kleene and Melitta Schachner",
year = "2003",
language = "English",
volume = "278",
pages = "10381--10388",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - The proprotein convertase PC5A and a metalloprotease are involved in the proteolytic processing of the neural adhesion molecule L1.

AU - Kalus, Ina

AU - Schnegelsberg, Birthe

AU - Seidah, Nabil G

AU - Kleene, Ralf

AU - Schachner, Melitta

PY - 2003

Y1 - 2003

N2 - The transmembrane and multidomain neural adhesion molecule L1 plays important functional roles in the developing and adult nervous system. L1 is proteolytically processed at two distinct sites within the extracellular domain, leading to the generation of different fragments. In this report, we present evidence that the proprotein convertase PC5A is the protease that cleaves L1 in the third fibronectin type III domain, whereas the proprotein convertases furin, PC1, PC2, PACE4, and PC7 are not effective in cleaving L1. Analysis of mutations revealed Arg(845) to be the site of cleavage generating the N-terminal 140-kDa fragment. This fragment was present in the hippocampus, which expresses PC5A, but was not detectable in the cerebellum, which does not express PC5A. The 140-kDa L1 fragment was found to be tightly associated with the full-length 200-kDa L1 molecule. The complex dissociated from the membrane upon cleavage by a protease acting at a more membrane-proximal site of full-length L1. This proteolytic cleavage was inhibited by the metalloprotease inhibitor GM 6001 and enhanced by a calmodulin inhibitor. L1-dependent neurite outgrowth of cerebellar neurons was inhibited by GM 6001, suggesting that proteolytic processing of L1 by a metalloprotease is involved in neurite outgrowth.

AB - The transmembrane and multidomain neural adhesion molecule L1 plays important functional roles in the developing and adult nervous system. L1 is proteolytically processed at two distinct sites within the extracellular domain, leading to the generation of different fragments. In this report, we present evidence that the proprotein convertase PC5A is the protease that cleaves L1 in the third fibronectin type III domain, whereas the proprotein convertases furin, PC1, PC2, PACE4, and PC7 are not effective in cleaving L1. Analysis of mutations revealed Arg(845) to be the site of cleavage generating the N-terminal 140-kDa fragment. This fragment was present in the hippocampus, which expresses PC5A, but was not detectable in the cerebellum, which does not express PC5A. The 140-kDa L1 fragment was found to be tightly associated with the full-length 200-kDa L1 molecule. The complex dissociated from the membrane upon cleavage by a protease acting at a more membrane-proximal site of full-length L1. This proteolytic cleavage was inhibited by the metalloprotease inhibitor GM 6001 and enhanced by a calmodulin inhibitor. L1-dependent neurite outgrowth of cerebellar neurons was inhibited by GM 6001, suggesting that proteolytic processing of L1 by a metalloprotease is involved in neurite outgrowth.

KW - Animals

KW - Mice

KW - Mice, Inbred C57BL

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Amino Acid Motifs

KW - Tumor Cells, Cultured

KW - Dimerization

KW - Serine Endopeptidases/physiology

KW - Cerebellum/metabolism

KW - Calmodulin/antagonists & inhibitors

KW - Fibronectins/metabolism

KW - Hippocampus/metabolism

KW - Metalloendopeptidases/physiology

KW - Neural Cell Adhesion Molecule L1/chemistry/metabolism

KW - Neurites/physiology

KW - Proprotein Convertase 5

KW - Animals

KW - Mice

KW - Mice, Inbred C57BL

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Amino Acid Motifs

KW - Tumor Cells, Cultured

KW - Dimerization

KW - Serine Endopeptidases/physiology

KW - Cerebellum/metabolism

KW - Calmodulin/antagonists & inhibitors

KW - Fibronectins/metabolism

KW - Hippocampus/metabolism

KW - Metalloendopeptidases/physiology

KW - Neural Cell Adhesion Molecule L1/chemistry/metabolism

KW - Neurites/physiology

KW - Proprotein Convertase 5

M3 - SCORING: Journal article

VL - 278

SP - 10381

EP - 10388

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 12

M1 - 12

ER -