Abstract
12-O-Tetradecanoylphorbol-13-acetate (TPA) activated the c-fos gene enhancer linked to the chloramphenicol acetyltransferase or luciferase reporter gene in the wild type PC-12 cells but not in the variant PC-12 cells that originated from the wild type cells. Transfection of the c-Ha-rasval12 complementary DNA (cDNA) or addition of dibutyryl cAMP to the wild type PC-12 cells as well as to the variant PC-12 cells activated the c-fos gene enhancer. Prolonged treatment of the wild type PC-12 cells with phorbol-12,13-dibutyrate caused down-regulation of protein kinase C. In these cells, TPA did not stimulate the c-fos gene enhancer any more, but transfection of the c-Ha-rasval12 cDNA still stimulated the c-fos gene enhancer to the same extent as induced in the control cells. Transfection of the c-Ha-rasval12 cDNA or addition of TPA to the wild type PC-12 cells stimulated the serum-response element but not the cAMP-response element. Dibutyryl cAMP stimulated both the serum-response element and the cAMP-response element in the wild type PC-12 cells. These results indicate that the c-Ha-rasval12 protein activates the serum-response element, but not the cAMP-response element in the c-fos gene enhancer, and that the signal pathway from the c-Ha-rasval12 protein to the c-fos serum-response element is independent of protein kinase C and cAMP-dependent protein kinase.
Highlights
Dibutyryl CAMP stimulated both the serum-response element and the CAMP-response element in the wild type PC- 12 cells. These results indicate that the c-Hava’12 protein activates the serum-response element iz not the CAMP-response element in the c-fos genl enhancer, and that the signal pathway from the c-Harag”e1l2 protein to the c-fos serum-response element is independent of protein kinase C and CAMP-dependent protein kinase
We have recently shown that the c-fos gene enhancer linked to the CAT reporter gene (c-fosCAT) is activated by protein kinase C and protein kinase A using the cDNAs of the constitutively active protein kinase C and the catalytic subunit of protein kinase A [16, 17]
This paper shows that the SRE rather than the CRE is responsible for the c-Ha-rasVs”’ p21-induced activation of the c-fos gene enhancer and that the signal pathway from rus ~21s to the c-fos SRE is independent of protein kinase C and protein kinase A
Summary
Genetic and biochemical analyses indicate that RASl and RAS2 proteins regulate CAMP levels through activation of adenylate cyclase [3]. The c-fos gene enhancer contains the SRE and CRE which are activated by TPA and Bt2cAMP, respectively (for a review, see Ref. 15). We attempted to explore the mode of action of rus p21s for c-fos gene activation in PC-12 cells using the cDNAs of the normal and activated rus ~21s to understand the intracellular signals transmitted from ras p21 to the nuclei. This paper shows that the SRE rather than the CRE is responsible for the c-Ha-rasVs”’ p21-induced activation of the c-fos gene enhancer and that the signal pathway from rus ~21s to the c-fos SRE is independent of protein kinase C and protein kinase A
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