Pro-domain in precursor nerve growth factor mediates cell death

被引：13

作者：

Armugam, Arunmozhiarasi ^{[1
]}

Koh, Dawn C. I. ^{[1
]}

Ching, Chai Siaw ^{[1
]}

Chandrasekaran, Karthikeyan ^{[1
]}

Kaur, Prameet ^{[1
]}

Jeyaseelan, Kandiah ^{[1
]}

机构：

[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore

来源：

NEUROCHEMISTRY INTERNATIONAL | 2012年 / 60卷 / 08期

基金：

英国医学研究理事会;

关键词：

Nerve growth factor; Pro-domain; Neurotrophic; Sortilin; Caspase; p75(NTR); Naja sputatrix; pro((R/G))NGF; trkA; NEURITE OUTGROWTH; NEUROTROPHINS; SURVIVAL; ACTIVATION; APOPTOSIS; PROTEINS; P75(NTR); SORTILIN; P75; RECEPTORS;

D O I：

10.1016/j.neuint.2012.03.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Nerve growth factor (NGF) is synthesized as a precursor, proNGF that undergoes post-translational processing to generate the biologically active mature NGF. While the neurotrophic function of NGF is well established, the activity of the proNGF precursor is still unclear. In this study, we have cloned the pro-domain of the precursor NGF molecule and have elucidated its function. We have used both mature and the furin resistant pro((R/G))NGF as controls in our experiments. Both pro((R/G))NGF and mature NGF (NGF) exhibited neurotrophic activity on PC12 cells while the pro-domain itself promoted cell death. The pro-domain, has been found to mediate apoptosis possibly by promoting the formation of a signaling complex comprising of endogenous p75(NTR) receptor, Bim/Bcl2 group of proteins and JNK and MEK1/2 signaling pathways. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：852 / 863

页数：12

共 50 条

[1]

Becker E.B., 2004, J NEUROSCI, V24, p[1, 9722]

[2]

Characterization of the c-Jun N-terminal kinase-BimEL signaling pathway in neuronal apoptosis [J].

Becker, EBE ;

Howell, J ;

Kodama, Y ;

Barker, PA ;

Bonni, A .

JOURNAL OF NEUROSCIENCE, 2004, 24 (40) :8762-8770

[3]

Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system [J].

Bibel, M ;

Barde, YA .

GENES & DEVELOPMENT, 2000, 14 (23) :2919-2937

[4]

Boersma AWM, 1996, CYTOMETRY, V24, P123, DOI 10.1002/(SICI)1097-0320(19960601)24:2<123::AID-CYTO4>3.0.CO

[5]

2-K

[6]

The p75NTR intracellular domain generated by neurotrophin-induced receptor cleavage potentiates Trk signaling [J].

Ceni, Claire ;

Kommaddi, Reddy Peera ;

Thomas, Rhalena ;

Vereker, Emily ;

Liu, Xiaoyang ;

McPherson, Peter S. ;

Ritter, Brigitte ;

Barker, Philip A. .

JOURNAL OF CELL SCIENCE, 2010, 123 (13) :2299-2307

[7]

Neurotrophins and their receptors: A convergence point for many signalling pathways [J].

Chao, MV .

NATURE REVIEWS NEUROSCIENCE, 2003, 4 (04) :299-309

[8]

Pulmonary inflammation and edema induced by phospholipase A2 -: Global gene analysis and effects on aquaporins and Na+/K+-ATPase [J].

Cher, CDN ;

Armugam, A ;

Lachumanan, R ;

Coghlan, MW ;

Jeyaseelan, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (33) :31352-31360

[9]

Human ProNGF: biological effects and binding profiles at TrkA, P75NTR and sortilin [J].

Clewes, Oliver ;

Fahey, Mark S. ;

Tyler, Sue J. ;

Watson, Judy J. ;

Seok, Heon ;

Catania, Caterina ;

Cho, Kwangwook ;

Dawbarn, David ;

Allen, Shelley J. .

JOURNAL OF NEUROCHEMISTRY, 2008, 107 (04) :1124-1135

[10]

A NERVE GROWTH-STIMULATING FACTOR ISOLATED FROM SNAKE VENOM [J].

COHEN, S ;

LEVIMONTALCINI, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1956, 42 (09) :571-&

← 1 2 3 4 5 →