Nishiyama U, Ubukata M, Magae J, Kataoka T, Erdödi F, Hartshorne D J, Isono K, Nagai K, Osada H
Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
Biosci Biotechnol Biochem. 1996 Jan;60(1):103-7. doi: 10.1271/bbb.60.103.
Tautomycin, a protein serine/threonine phosphatase inhibitor, was chemically degraded, and five derivatives were investigated for their biological activities. None of them exerted any inhibitory effects on the activity of protein phosphatase types 1 and 2A. However, one derivative, named TM2a, induced a significant morphological change (bleb-formation) of human myeloid leukemia K562 cells. TM2b, the trimethyl ester of TM2, did not induce bleb-formation. Thus, the maleic anhydride structure played an important role in the biological activity. The biological properties of TM2a toward K562 cells resembled those of a phorbol ester, rather than of tautomycin. The phorbol ester-induced bleb formation was abrogated by a non-specific inhibitor of protein kinases, staurosporine, and by an inhibitor of protein kinase C (PKC), H-7, but TM2a-induced bleb formation was abrogated only by staurosporine. Enhanced phosphorylation of the two proteins was observed after their exposure to TM2a. This suggest that the effect was not due to any inhibition of protein phosphatase 1 or 2A, but rather to the activation of an unidentified kinase, possibly of the PKC family, or to inhibition of a protein phosphatase other than type 1 or 2A.
陶氏霉素是一种蛋白质丝氨酸/苏氨酸磷酸酶抑制剂，对其进行化学降解，并研究了五种衍生物的生物活性。它们均未对1型和2A型蛋白质磷酸酶的活性产生任何抑制作用。然而，一种名为TM2a的衍生物诱导人髓系白血病K562细胞发生了显著的形态变化（形成泡状）。TM2的三甲酯TM2b未诱导形成泡状。因此，马来酸酐结构在生物活性中起重要作用。TM2a对K562细胞的生物学特性类似于佛波酯，而非陶氏霉素。佛波酯诱导的泡状形成可被蛋白激酶的非特异性抑制剂星形孢菌素以及蛋白激酶C（PKC）抑制剂H-7消除，但TM2a诱导的泡状形成仅被星形孢菌素消除。在两种蛋白质暴露于TM2a后，观察到它们的磷酸化增强。这表明该效应并非由于对1型或2A型蛋白质磷酸酶的任何抑制，而是由于一种未鉴定的激酶（可能是PKC家族）的激活，或者是由于对1型或2A型以外的蛋白质磷酸酶的抑制。
