Evans J P, Wickremasinghe R G, Hoffbrand A V
Department of Haematology, Royal Free Hospital School of Medicine, London, U.K.
Leukemia. 1987 Nov;1(11):782-5.
Kinases which phosphorylate proteins on tyrosine residues are of importance in the control of both normal and malignant cell proliferation. The receptors for a number of growth factors have intracellular domains with tyrosine protein kinase activity and several viral oncogenes code for tyrosine protein kinases. An abnormal tyrosine protein kinase has been implicated in the pathogenesis of chronic granulocytic leukemia. Using an immunoblot method and an antiphosphotyrosine antibody, we have detected substrates of tyrosine protein kinases in fresh human leukemia cells and normal blood and bone marrow cells. These substrates were present in all types of cells examined. Cells from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic lymphocytic leukemia contain prominent phosphotyrosine-containing protein bands with molecular weights in excess of 95 kDa. By contrast, chronic granulocytic leukemia cells, as well as normal bone marrow cells, lymphocytes, and monocytes, contain predominantly low molecular weight (less than 95 kDa) tyrosine kinase substrates. When lymphocytes were stimulated to enter cell cycle, however, high molecular weight substrates of similar molecular weights to those detected in acute lymphoblastic leukemia, acute myeloid leukemia, and chronic lymphocytic leukemia became prominent. The implications of these findings in the control of normal and malignant cell proliferation and differentiation are discussed.
能使蛋白质酪氨酸残基磷酸化的激酶在正常和恶性细胞增殖的调控中都很重要。许多生长因子的受体具有胞内酪氨酸蛋白激酶活性结构域，并且一些病毒癌基因编码酪氨酸蛋白激酶。一种异常的酪氨酸蛋白激酶与慢性粒细胞白血病的发病机制有关。我们使用免疫印迹法和抗磷酸酪氨酸抗体，在新鲜的人类白血病细胞以及正常血液和骨髓细胞中检测到了酪氨酸蛋白激酶的底物。这些底物存在于所有检测的细胞类型中。急性淋巴细胞白血病、急性髓细胞白血病和慢性淋巴细胞白血病患者的细胞含有明显的含磷酸酪氨酸的蛋白条带，其分子量超过95 kDa。相比之下，慢性粒细胞白血病细胞以及正常骨髓细胞、淋巴细胞和单核细胞主要含有低分子量（小于95 kDa）的酪氨酸激酶底物。然而，当淋巴细胞被刺激进入细胞周期时，与在急性淋巴细胞白血病、急性髓细胞白血病和慢性淋巴细胞白血病中检测到的分子量相似的高分子量底物变得明显。本文讨论了这些发现对正常和恶性细胞增殖与分化调控的意义。
