| First Author | Murray NR | Year | 2004 |
| Journal | J Cell Biol | Volume | 164 |
| Issue | 6 | Pages | 797-802 |
| PubMed ID | 15024028 | Mgi Jnum | J:89285 |
| Mgi Id | MGI:3039325 | Doi | 10.1083/jcb.200311011 |
| Citation | Murray NR, et al. (2004) Protein kinase Ciota is required for Ras transformation and colon carcinogenesis in vivo. J Cell Biol 164(6):797-802 |
| abstractText | Protein kinase C iota (PKCiota) has been implicated in Ras signaling, however, a role for PKCiota in oncogenic Ras-mediated transformation has not been established. Here, we show that PKCiota is a critical downstream effector of oncogenic Ras in the colonic epithelium. Transgenic mice expressing constitutively active PKCiota in the colon are highly susceptible to carcinogen-induced colon carcinogenesis, whereas mice expressing kinase-deficient PKCiota (kdPKCiota) are resistant to both carcinogen- and oncogenic Ras-mediated carcinogenesis. Expression of kdPKCiota in Ras-transformed rat intestinal epithelial cells blocks oncogenic Ras-mediated activation of Rac1, cellular invasion, and anchorage-independent growth. Constitutively active Rac1 (RacV12) restores invasiveness and anchorage-independent growth in Ras-transformed rat intestinal epithelial cells expressing kdPKCiota. Our data demonstrate that PKCiota is required for oncogenic Ras- and carcinogen-mediated colon carcinogenesis in vivo and define a procarcinogenic signaling axis consisting of Ras, PKCiota, and Rac1. |
