Leevers S J, Weinkove D, MacDougall L K, Hafen E, Waterfield M D
Ludwig Institute for Cancer Research, London, UK.
EMBO J. 1996 Dec 2;15(23):6584-94.
Phosphoinositide 3-kinases (PI3Ks) have been identified in an evolutionarily diverse range of organisms, including mammals, Drosophila, yeast, plants and Dictyostelium. They are activated by a multitude of extracellular signals and implicated in mitogenesis, differentiation and cell survival, as well as in the control of the cytoskeleton and cell shape. Here we describe the molecular and functional analysis of Drosophila p110 (Dp110). A full-length Dp110 cDNA was isolated and found to encode a protein homologous throughout its length to the class I mammalian PI3Ks p110alpha and p110beta. Overexpression of Dp110 in wing or eye imaginal discs resulted in flies with enlarged wings or eyes respectively. In contrast, overexpression of Dp110 containing a mutation predicted to result in the loss of catalytic activity resulted in smaller wings and eyes. The alterations in wing size result from changes in both cell size and cell number, whereas in the eye only differences in cell size were detected. These data imply a role for Dp110 in growth control during Drosophila development and have implications for the function of class I PI3Ks in other organisms.
磷脂酰肌醇3激酶(PI3Ks)已在包括哺乳动物、果蝇、酵母、植物和盘基网柄菌在内的多种进化上不同的生物体中被鉴定出来。它们被多种细胞外信号激活,并参与有丝分裂、分化和细胞存活,以及细胞骨架和细胞形状的控制。在这里,我们描述了果蝇p110(Dp110)的分子和功能分析。分离出了全长Dp110 cDNA,发现其编码的蛋白质在整个长度上与I类哺乳动物PI3Ks p110α和p110β同源。在翅或眼成虫盘过度表达Dp110分别导致果蝇翅膀或眼睛变大。相反,过度表达含有预测会导致催化活性丧失的突变的Dp110会导致翅膀和眼睛变小。翅大小的改变是由细胞大小和细胞数量的变化引起的,而在眼中仅检测到细胞大小的差异。这些数据表明Dp110在果蝇发育过程中的生长控制中起作用,并对I类PI3Ks在其他生物体中的功能有影响。