Byrd J C, Lichti U
J Biol Chem. 1987 Aug 25;262(24):11699-705.
Transglutaminases are a class of enzymes capable of covalently cross-linking both intracellular and extracellular proteins. The activity of tissue transglutaminase is known to decrease precipitously following neoplastic transformation, and it has been hypothesized that transglutaminase may be involved in growth regulation. We have found that the differentiation promoter sodium butyrate is able to cause a marked increase in transglutaminase activity in PC12 pheochromocytoma cells in a time- and dose-dependent manner. This increased transglutaminase activity is associated with growth arrest, as well as with striking morphological changes including increased cell adhesion. The transglutaminase induced by sodium butyrate appears to be tissue transglutaminase, based on its cytosolic localization, thermal lability at basic pH, and elution profile on anion-exchange chromatography. Untreated PC12 cells contain only small amounts of transglutaminase which resembles epidermal transglutaminase, an enzyme previously described only in skin. In contrast to sodium butyrate, nerve growth factor did not stimulate tissue transglutaminase in PC12 cells, although it, too, caused growth arrest. It is hypothesized that transglutaminase may be involved in certain morphological changes accompanying cellular differentiation and neoplastic transformation, rather than in growth regulation per se.
转谷氨酰胺酶是一类能够使细胞内和细胞外蛋白质发生共价交联的酶。已知组织转谷氨酰胺酶的活性在肿瘤转化后会急剧下降,并且有人推测转谷氨酰胺酶可能参与生长调节。我们发现分化促进剂丁酸钠能够以时间和剂量依赖的方式使PC12嗜铬细胞瘤细胞中的转谷氨酰胺酶活性显著增加。这种增加的转谷氨酰胺酶活性与生长停滞以及包括细胞黏附增加在内的显著形态学变化相关。基于其胞质定位、在碱性pH下的热不稳定性以及阴离子交换色谱上的洗脱图谱,丁酸钠诱导的转谷氨酰胺酶似乎是组织转谷氨酰胺酶。未处理的PC12细胞仅含有少量类似于表皮转谷氨酰胺酶的转谷氨酰胺酶,表皮转谷氨酰胺酶是一种以前仅在皮肤中描述过的酶。与丁酸钠相反,神经生长因子虽然也会导致生长停滞,但它不会刺激PC12细胞中的组织转谷氨酰胺酶。据推测,转谷氨酰胺酶可能参与伴随细胞分化和肿瘤转化的某些形态学变化,而不是本身参与生长调节。