+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn

+ Translate
+ Recently Requested

The effect of sphingosine and phorbol ester on the signal transduction enzymes and fibronectin release in cell culture

The effect of sphingosine and phorbol ester on the signal transduction enzymes and fibronectin release in cell culture

Biochimica et Biophysica Acta 1135(3): 295-300

In testing the hypothesis that the stimulation of the release of fibronectin (FN) by 12-O-tetradecanoylphorbol 13-acetate (TPA) from human lung fibroblasts in culture is the result of activation of protein kinase C (PKC), we found that the PKC inhibitor sphingosine strongly inhibited FN release in presence and even in absence of TPA. However, a different PKC inhibitor, calphostin C, despite almost complete inhibition of PKC, had no effect on FN release. We concluded that sphingosine is a potent inhibitor of FN release from the cell surface, independent of its inhibition of PKC; and that TPA stimulates release of FN by a pathway other than activation of PKC. We found that the activation of PKC by TPA was accompanied by inhibition of the cAMP-dependent protein kinase (PKA). When PKA was inhibited by an antagonist (H8, a cAMP analogue) at a concentration specific for PKA inhibition, the release of FN was stimulated similar to the stimulation with TPA. Activation of PKA with forskolin resulted in decreased FN release. In conclusion, we have shown that: (1) sphingosine had a robust effect inhibiting the release of FN from fibroblasts, independent of its action on PKC; (2) TPA treatment of these cells resulted in inhibition of PKA; (3) inhibition of PKA stimulated FN release whereas its activation decreased this release. It is possible that PKA, by phosphorylating a protein, may function, directly or indirectly, in keeping FN attached to the cell surface of fibroblasts.

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

Accession: 007892371

Download citation: RISBibTeXText

PMID: 1377951

DOI: 10.1016/0167-4889(92)90234-3

Related references

Signal transduction in phorbol ester-sensitive and resistant EL4 cell lines. FASEB Journal 8(7): A1234, 1994

Early phorbol ester induced release of cell surface fibronectin: direct observation by photoelectron microscopy. European Journal of Cell Biology 41(2): 222-229, 1986

Sphingosine kinase 1 activation and translocation to the plasma membrane in a protein kinase C dependent manner Phorbol ester mediated extracellular release of sphingosine-1-phosphate. Molecular Biology of the Cell 13(Supplement): 367a, 2002

Inhibitory effect of phorbol ester on carbachol-induced signal transduction in cultured canine tracheal smooth muscle cells. Journal Of Biomedical Science. 2(3): 283-292, 1995

Regulation of the neurotransmitter release machinery by signal transduction pathways expressing unregulated signal transduction enzymes and parvalbumin in axon terminals from hsv 1 vectors. Society for Neuroscience Abstracts 17(1-2): 603, 1991

Isoform selective protein kinase C inhibitors have no effect on phorbol ester facilitation of norepinephrine release from rat atria and brain cortex or phorbol ester induced phosphorylation of GAP-43. Society for Neuroscience Abstracts 27(1): 1016, 2001

Phorbol ester-induced expression of airway squamous cell differentiation marker, SPRR1B, is regulated by protein kinase Cd/Ras/MEKK1/MKK1-dependent/AP-1 signal transduction pathway. The Journal of Biological Chemistry 275(41): 250-9, 2000

Phorbol ester enhances CO2 signal transduction in avian intrapulmonary chemoreceptors. FASEB Journal 12(4): A169, March 17, 1998

Effects of retinoic acid on phorbol ester signal transduction and differentiation. Journal of Cancer Research & Clinical Oncology 116(SUPPL PART 2): 977, 1990

Phorbol ester-induced expression of airway squamous cell differentiation marker, SPRR1B, is regulated by protein kinase Cdelta /Ras/MEKK1/MKK1-dependent/AP-1 signal transduction pathway. Journal of Biological Chemistry 275(41): 32250-9, 2000

Signal transduction in SF9 insect cells: endocytosis of recombinant CD4 after phorbol ester treatment. Biochemical and Biophysical Research Communications 207(1): 411-416, 1995

Mechanisms of signal transduction in phorbol ester responsive murine peritoneal b lymphocytes. Journal of Cellular Biochemistry Supplement (14 PART D): 254, 1990

PKC-dependent JNK activation by phorbol ester is regulated by a Ras- and/or a Rac1-mediated signal transduction pathways. FASEB Journal 15(5): A904, March 8, 2001

Phorbol ester effects on adrenergic hormone signal transduction in normal and h ras transformed cells. Strand, F L (Ed ) Annals Of The New York Academy Of Sciences, Vol 494 Third Colloquium in Biological Sciences: Cellular Signal Transduction; New York, New York, Usa, November 4, 1985 Xvii+455p The New York Academy Of Sciences: New York, New York, Usa Illus 111-113, 1987