亚硝胺诱发大鼠肝癌不同细胞组分中三类蛋白激酶的变化

CHANGES IN THREE KINDS OF PROTEIN KINASE IN DIFFERENT SUBCELLULAR FRACTIONS OF INDUCED RAT HEPATOCARCINOMA

作者研究了正常大鼠肝三个亚细胞组分中酪氨酸蛋白激酶（ＴＰＫ）、蛋白檄酶Ａ（ＰＫＡ）和蛋白激酶Ｃ（ＰＫＣ）的活力和亚硝胺诱发大鼠肝癌后这些蛋白激酶的变化。发现正常鼠肝中的ＴＰＫ的活力为胞核＞膜性结构＞胞液，ＰＫＡ为胞液＞膜结构＞胞核，而ＰＫＣ则为膜结构＞胞液＞胞核。在胞液的三类蛋白激酶中，ＰＫＣ＞ＰＫＡ＞ＴＰＫ；膜结构为ＰＫＣ＞ＴＰＫ＞ＰＫＡ；而胞核却以ＴＰＫ特别高，ＰＫＡ和ＰＫＣ的含量甚微。ＤＥＮ诱发大鼠肝癌１８周后，膜性和胞核ＴＰＫ升高，尤以膜性ＴＰＫ升高明显。但膜性ＰＫＡ则降低而胞核ＰＫＡ升高，胞液中ＴＰＫ和ＰＫＡ均无明显变化；而ＰＫＣ和ＴＰＫ相反，胞液中显著升高，膜性及胞核变化不大。其中ＰＫＣ的增高不是激活剂含量上升的结果。

Activities of tyrosine protein kinase(TPK),protein kinase A(PKA)and protein kinase C(PKC) in three different subcellular fractions of the normal rat liver and N-nitrosodiethylamine(DEN)induced rat hepatocarcinoma cells were studied.It was found that in normal rat liver.the activity of TPK was nuelear>membranous>cytosolic;the activity of PKA was cytosolic>membranous>nuclear;and for PKC,membranous>cytosolic>nuclear.In the cytosolic fraction,the activity gradient of the protein kinases were PKC>PKA>TPK.In the membranous fraetion,PKC>TPK>PKA.However,in the nuclear fraction.only TPK activity was high, that of PKA and PKC were very low.After 18 weeks following the date of hepatocarcinogenic induction,the membranous and nuclear TPK,especially the former,markedly elevated. The membranous PKA decreased and nuclear PKA increased.The cytosolie TPK and PKA were not significantly changed.PKC was increased only in the cytosolic fraction but not in the membranous or nuclear.The changes of protein kinases mentioned above were probably due to changes of gene expression, but not the results of intracellular translocation of the enzymes,nor increases of the activators or their precursors as for PKC.