Woodgett J R, Kyriakis J M, Avruch J, Zon L I, Zanke B, Templeton D J
Ontario Cancer Institute, Toronto, Canada.
Philos Trans R Soc Lond B Biol Sci. 1996 Feb 29;351(1336):135-41; discussion 142. doi: 10.1098/rstb.1996.0009.
Mammalian cells respond to their immediate environment by inducing signal transduction cascades that regulate metabolism, secretion and gene expression. Several of these signalling pathways are structurally and organizationally related insofar as they require activation of a protein-serine kinase via it's phosphorylation on tyrosine and threonine; the archetype being mitogen-activated protein kinase (MAPK) which responds primarily to mitogenic stimuli via Ras. In contrast, two more recently identified cascades are responsive to cellular stresses such as heat, inflammatory cytokines, ischaemia and metabolic poisons. The recent identification of the components of these pathways has allowed manipulation of the stress-responsive pathways and evaluation of their physiological roles. These studies reveal a high degree of independence between the pathways not apparent from in vitro studies. Manipulation of the pathways in vivo will likely result in novel therapies for inflammatory disease and reperfusion injury.
哺乳动物细胞通过诱导调节代谢、分泌和基因表达的信号转导级联反应来响应其周围环境。这些信号通路中有几条在结构和组织上相关，因为它们需要通过酪氨酸和苏氨酸磷酸化来激活蛋白丝氨酸激酶；原型是丝裂原活化蛋白激酶（MAPK），它主要通过Ras对有丝分裂刺激作出反应。相比之下，最近发现的另外两条级联反应对热、炎性细胞因子、缺血和代谢毒物等细胞应激作出反应。这些通路成分的最新发现使得能够对应激反应通路进行调控并评估其生理作用。这些研究揭示了这些通路之间高度的独立性，这在体外研究中并不明显。在体内对这些通路进行调控可能会带来针对炎症性疾病和再灌注损伤的新疗法。
