title: Pro-domain in precursor nerve growth factor mediates cell death.
abstract: 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.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Arunmozhiarasi
authors.initials: A
authors.lastname: Armugam
authors.forename: Dawn C I
authors.initials: DC
authors.lastname: Koh
authors.forename: Chai Siaw
authors.initials: CS
authors.lastname: Ching
authors.forename: Karthikeyan
authors.initials: K
authors.lastname: Chandrasekaran
authors.forename: Prameet
authors.initials: P
authors.lastname: Kaur
authors.forename: Kandiah
authors.initials: K
authors.lastname: Jeyaseelan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D009414:Nerve Growth Factors