Cooper J A, Simon M A, Kussick S J
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Cell Growth Differ. 1996 Nov;7(11):1435-41.
Vertebrate Src can be activated by specific mutations to become oncogenic. Analogous mutations in Drosophila Src64 (DSrc) induce abnormal differentiation of photoreceptor cells when expressed ectopically in the developing Drosophila adult eye. We have investigated the roles that the adapter protein, Downstream of receptor kinases (Drk), and the SH2 domain-containing tyrosine phosphatase, Corkscrew (Csw), play in this process. We find that dominant-negative mutations in either the drk or csw genes ameliorate the developmental abnormalities induced by activated DSrc. This suggests that Drk and Csw are required downstream of, or parallel to, DSrc. Csw does not act solely as an upstream activator of DSrc. The results are discussed in relation to potential roles for the vertebrate homologues of Drk and Csw (Grb2 and SHP2, respectively) in the transformation of fibroblasts by vertebrate Src.
脊椎动物的Src可通过特定突变被激活而成为致癌基因。果蝇Src64（DSrc）中的类似突变，当在发育中的果蝇成虫眼睛中异位表达时，会诱导光感受器细胞异常分化。我们研究了衔接蛋白受体激酶下游（Drk）和含SH2结构域的酪氨酸磷酸酶螺旋钻（Csw）在此过程中所起的作用。我们发现，drk或csw基因中的显性负性突变可改善由活化的DSrc诱导的发育异常。这表明Drk和Csw在DSrc下游或与之平行发挥作用。Csw并非仅作为DSrc的上游激活剂起作用。我们还讨论了这些结果与Drk和Csw的脊椎动物同源物（分别为Grb2和SHP2）在脊椎动物Src转化成纤维细胞过程中的潜在作用。
