First Author | Singhal SS | Year | 2006 |
Journal | Biochem Biophys Res Commun | Volume | 348 |
Issue | 2 | Pages | 722-7 |
PubMed ID | 16890208 | Mgi Jnum | J:111986 |
Mgi Id | MGI:3655323 | Doi | 10.1016/j.bbrc.2006.07.118 |
Citation | Singhal SS, et al. (2006) Mitogenic and drug-resistance mediating effects of PKCalpha require RLIP76. Biochem Biophys Res Commun 348(2):722-7 |
abstractText | PKCalpha-activation is a key signaling event governing cell growth, stress-resistance, and drug-resistance. Our recent studies demonstrated that DOX-resistance mediating effects of PKCalpha require the presence of RLIP76, and their concerted action is sufficient to explain intrinsic DOX-resistance of NSCLC [S.S. Singhal, D. Wickramarachchi, J. Singhal, S. Yadav, Y.C. Awasthi, et al., Determinants of differential doxorubicin sensitivity between SCLC and NSCLC. FEBS Lett. 580 (2006) 2258-2264]. Present studies were carried out to further explore the suggestion from the previous studies that the mitogenic effects of PKCalpha also require RLIP76. RLIP76-/- MEFs were resistant to PKCalpha-depletion mediated growth inhibition, as well as to the PKCalpha-dependent mitogen, phorbol 12-myristate 13-acetate (PMA). Augmenting cellular levels of RLIP76 using purified recombinant RLIP76 increased growth rate in all cells, and restored the sensitivity of RLIP76-/- MEFs to both inhibition through PKCalpha-depletion and stimulation through PMA. These results show that RLIP76 is a necessary down-stream effector for PKCalpha-mediated mitogenesis. |