+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Plasminogen gene expression is regulated by nerve growth factor

Plasminogen gene expression is regulated by nerve growth factor

Journal of Thrombosis and Haemostasis 5(8): 1715-1725

Studies have documented a requirement for an intact plasminogen (Plg) activation system in neurite outgrowth induced by nerve growth factor (NGF). In this study we addressed the effect of NGF on Plg synthesis in model NGF-responsive PC-12 cells. The effect of NGF on Plg gene expression was assessed using Western blotting, quantitative polymerase chain reaction, luciferase reporter assays, site directed mutagenesis, electrophoretic mobility shift assays and chromatin immunoprecipitation. NGF treatment increased Plg expression 3-fold and steady state levels of Plg mRNA were increased 6.82-fold. This effect also was observed in cortical neurons. PC-12 cells transfected with a luciferase reporter gene under the control of a 2400 bp fragment of the murine Plg promoter exhibited a 5-fold increase in luciferase activity following treatment with NGF. This response was dependent on Ras/ERK and PI3 K signaling because treatment with PD98059 together with wortmannin decreased promoter activity, in response to NGF, to the level exhibited by untreated cells. Furthermore, co-transfection with a dominant-negative mutant Ha-Ras completely blocked NGF-induced luciferase activity. In deletional and mutational studies we identified two Sp1 binding sites located between nucleotides -255 and -106 of the Plg promoter that were required for the full response of the Plg promoter to NGF. In chromatin immunoprecipitation assays the Sp1 transcription factor bound to the endogenous Plg promoter. These results suggest that Plg gene expression is up-regulated by neurotrophins that may provide a previously unrecognized mechanism for enhancing the effects of neurotrophins via the proteolytic activity of plasmin.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 055023066

Download citation: RISBibTeXText

PMID: 17663741

DOI: 10.1111/j.1538-7836.2007.02636.x

Related references

Nerve growth factor regulated gene expression in pc 12 cells. Society for Neuroscience Abstracts 12(1): 214, 1986

Beta1 adducin gene expression in DRG is developmentally regulated and is upregulated by glial-derived neurotrophic factor and nerve growth factor. Brain Research. Molecular Brain Research 90(2): 118-124, 2001

Developmentally regulated expression of the nerve growth factor receptor gene in the periphery and brain. Proceedings of the National Academy of Sciences of the United States of America 84(9): 3060-3063, 1987

CDNA microarray analysis of nerve growth factor-regulated gene expression profile in rat PC12 cells. Neurochemical Research 30(4): 533-540, 2005

Identification of diverse nerve growth factor-regulated genes by serial analysis of gene expression (SAGE) profiling. Proceedings of the National Academy of Sciences of the United States of America 97(19): 10424-9, 2000

SH2B1beta (SH2-Bbeta) enhances expression of a subset of nerve growth factor-regulated genes important for neuronal differentiation including genes encoding urokinase plasminogen activator receptor and matrix metalloproteinase 3/10. Molecular Endocrinology 22(2): 454-476, 2008

Damage-induced neuronal endopeptidase (DINE/ECEL) expression is regulated by leukemia inhibitory factor and deprivation of nerve growth factor in rat sensory ganglia after nerve injury. Journal of Neuroscience 22(21): 9410-9418, 2002

Degeneration of rat cholinergic basal forebrain neurons and reactive changes in nerve growth factor expression after chronic neurotoxic injury--II. Reactive expression of the nerve growth factor gene in astrocytes. Neuroscience 65(3): 647-659, 1995

Nerve growth factor- and epidermal growth factor-regulated gene transcription in PC12 pheochromocytoma and INS-1 insulinoma cells. European Journal of Cell Biology 79(12): 924-935, 2000

Regulation of nerve growth factor receptor gene expression by nerve growth factor in the developing peripheral nervous system. Journal of Cell Biology 112(2): 303-312, 1991

Nerve Growth Factor Regulates Expression of the Nerve Growth Factor Receptor Gene in Adult Sensory Neurons. European Journal of Neuroscience 2(5): 389-396, 1990

Activation of extracellular signal-regulated protein kinase 5 is essential for cystitis- and nerve growth factor-induced calcitonin gene-related peptide expression in sensory neurons. Molecular Pain 8: 48, 2012

The expression of interleukin-6 and its receptor in Schwann cells and sciatic nerve is regulated by 18 KD fibroblast growth factor-2 and nerve lesion. Society for Neuroscience Abstracts 24(1-2): 1538, 1998

Expression of nerve growth factor receptor ngfr messenger rna in the rat retina is developmentally regulated and increased after optic nerve section. Society for Neuroscience Abstracts 16(1): 826, 1990

1,25-dihydroxyvitamin D-3 regulates the expression of nerve growth factor via an AP-1 sequence in the nerve growth factor gene. Journal of Investigative Medicine 45(3): 249A, 1997