Two different signal transduction pathways can be activated by transforming growth factor β1 in epithelial cells Journal Article
| Authors: | Yan, Z.; Winawer, S.; Friedman, E. |
| Article Title: | Two different signal transduction pathways can be activated by transforming growth factor β1 in epithelial cells |
| Abstract: | Signal transduction initiated by transforming growth factor β1 (TGFβ1) was studied in two sublines of the same colon carcinoma cell line, which respond in opposite ways to TGFβ1, by proliferation or by growth inhibition. TGFβ1 activates ras proteins within 5 min of addition when it acts to inhibit growth but not when it acts as a mitogen. In both cases TGFβ1 also rapidly modulates the activities of three protein kinases, detected by their in gel kinase activity on the mitogen-activated protein kinase (MAP kinase) substrate, myelin basic protein (MBP). When TGFβ1 acts as a mitogen for U9 cells, it increases the activity of MBP kinases of 57, 105, and 130 kDa within 10 min of the addition without detectably activating ras proteins. When TGFβ1 inhibits the growth of HD3 cells, it activates ras proteins and the 57-kDa MBP kinase within 5 min but inhibits the activity of the 105- and 130-kDa MBP kinases. In HD3 cells ras activation occurred in two signal transduction pathways, one from TGFβ1 leading to growth inhibition and one from epidermal growth factor (EGF) leading to proliferation. In addition to ras proteins, EGF activates a different set of MBP kinases in HD3 cells than does TGFβ1, MBP kinases of 85, 57, and 44 kDa. The latter is likely to be the 44-kDa MAP kinase extracellular signal-regulated kinase (erk) 1, because EGF treatment of HD3 cells activates erk1 by increasing its phosphotyrosine level. Therefore, in two closely related epithelial cell lines TGFβ1 activates two different signal transduction pathways, one ras-dependent and one ras-independent, and modulates the activities of a set of MBP kinases. |
| Keywords: | signal transduction; epidermal growth factor; human cell; cell proliferation; cell division; gene expression; transforming growth factor beta; cell line; enzyme activation; tumor cells, cultured; enzyme activity; enzyme regulation; transforming growth factor beta1; epithelium cell; epithelial cells; oncogene protein p21(ras); ras protein; epithelium; colon carcinoma; protein kinase; growth inhibition; ca(2+)-calmodulin dependent protein kinase; human; priority journal; article; support, u.s. gov't, p.h.s.; oncogene c fos |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 269 |
| Issue: | 18 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1994-05-06 |
| Start Page: | 13231 |
| End Page: | 13237 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 8175753 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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