Sicard R E
Department of Surgery, University of Minnesota, Minneapolis 55455.
Prog Clin Biol Res. 1993;383A:223-31.
Traditional signal transduction pathways appear to be operating during amphibian forelimb regeneration, as in other developing systems. A consistent picture appears to be developing that suggests that growth factors promoting proliferation during regeneration act through cAMP-independent mechanisms while factors that modulate differentiation and morphogenesis include signaling pathways in which cAMP participates. Although our understanding of these pathways is far from complete, it is becoming increasingly evident that further characterization of signal transduction events will facilitate (a) identifying major signaling substances, (b) determining the cellular events in regeneration that they modulate, and (c) defining the mechanisms through which they act. The present study demonstrates that PPtases, and in particular PTPases, can be studied in regenerating newt limbs. More importantly, this investigation demonstrates that there are progressive and significant increases in PPtase activity during regeneration. Moreover, the observed patterns of PPtase activity during regeneration conform to an emerging picture that ligands acting through receptors possessing intrinsic tyrosine kinase activity promote proliferation within the regeneration blastema. However, the substrates used in this study precluded acquiring insights about modulating effects of serine/threonine kinases (e.g., PKA and PKC). Nevertheless, these data suggest that activation of PPtases contribute to the orchestration of the diverse cellular activities required to regenerate a vertebrate appendage.
与其他发育系统一样,传统的信号转导途径似乎在两栖动物前肢再生过程中发挥作用。一幅连贯的图景似乎正在形成,这表明在再生过程中促进增殖的生长因子通过不依赖cAMP的机制起作用,而调节分化和形态发生的因子则包括cAMP参与的信号通路。尽管我们对这些途径的理解还远未完整,但越来越明显的是,对信号转导事件的进一步表征将有助于:(a)识别主要的信号物质;(b)确定它们在再生过程中调节的细胞事件;(c)定义它们发挥作用的机制。本研究表明,可以在蝾螈肢体再生过程中研究蛋白磷酸酶,特别是蛋白酪氨酸磷酸酶。更重要的是,这项研究表明在再生过程中蛋白磷酸酶活性有逐渐且显著的增加。此外,在再生过程中观察到的蛋白磷酸酶活性模式符合一种新出现的图景,即通过具有内在酪氨酸激酶活性的受体起作用的配体促进再生芽基内的增殖。然而,本研究中使用的底物妨碍了我们了解丝氨酸/苏氨酸激酶(如蛋白激酶A和蛋白激酶C)的调节作用。尽管如此,这些数据表明蛋白磷酸酶的激活有助于协调再生脊椎动物附肢所需的各种细胞活动。