Keating M T, Williams L T
Howard Hughes Medical Institute, San Francisco, CA.
Science. 1988 Feb 19;239(4842):914-6. doi: 10.1126/science.2829358.
Autocrine activation of platelet-derived growth factor (PDGF) receptors is the mechanism of transformation by the v-sis oncogene. Since the addition of PDGF does not transform normal cells, autocrine mechanisms may involve unique pathways of receptor activation. In this study autocrine stimulation of the PDGF receptor was observed in v-sis-transformed normal rat kidney (NRK) cells. In contrast to receptor activation in normal cells, autocrine activation of PDGF receptors in v-sis-transformed cells occurred in intracellular compartments, disrupting receptor processing and diverting receptors and their precursors to a chloroquine-sensitive degradation pathway. These findings show that intracellular activation of receptors by autocrine mechanisms may play a role in cell transformation.
血小板源性生长因子(PDGF)受体的自分泌激活是v-sis癌基因导致细胞转化的机制。由于添加PDGF并不能使正常细胞发生转化,因此自分泌机制可能涉及受体激活的独特途径。在本研究中,在v-sis转化的正常大鼠肾(NRK)细胞中观察到了PDGF受体的自分泌刺激。与正常细胞中的受体激活不同,v-sis转化细胞中PDGF受体的自分泌激活发生在细胞内区室,破坏了受体加工过程,并使受体及其前体转向对氯喹敏感的降解途径。这些发现表明,自分泌机制导致的受体细胞内激活可能在细胞转化中起作用。