Millán J L
La Jolla Cancer Research Foundation, Cancer Research Center, La Jolla, California 92037.
Anticancer Res. 1988 Sep-Oct;8(5A):995-1004.
Alkaline phosphatases (APs) are members of a multigene family, that in humans include four different genes. Their wide distribution in nature, ranging from bacteria to man, indicates that APs are involved in fundamental biochemical processes. Information on the primary structure of eukaryotic APs is accumulating very rapidly. There is a high degree of similarity between the eukaryotic APs and Escherichia coli AP. Structural comparisons with the E. coli enzyme have helped identify those residues that may participate in the active site pocket, as well as predict functional-structural features unique to eukaryotic APs. The general structure of the AP genes has now been revealed through the cloning of the germ cell AP gene in humans. The entire nucleotide sequence of the gene reveals the existence of 11 exons interrupted by 10 small introns. Elucidation of the mechanism of regulation and tissue-specific expression of AP genes will be highly relevant to understanding the re-expression of these enzymes in testicular and ovarian tumors. Two vitally important developmental processes, i.e., germ cell differentiation and early embryogenesis, provide experimentally accessible models to attempt to unravel the elusive function of APs.
碱性磷酸酶(APs)是一个多基因家族的成员,在人类中包括四个不同的基因。它们在自然界广泛分布,从细菌到人类,这表明APs参与了基本的生化过程。关于真核生物APs一级结构的信息正在迅速积累。真核生物APs与大肠杆菌AP之间存在高度相似性。与大肠杆菌酶的结构比较有助于确定可能参与活性位点口袋的那些残基,并预测真核生物APs特有的功能结构特征。现在通过克隆人类生殖细胞AP基因揭示了AP基因的一般结构。该基因的完整核苷酸序列显示存在11个外显子,被10个小内含子打断。阐明AP基因的调控机制和组织特异性表达将与理解这些酶在睾丸和卵巢肿瘤中的重新表达高度相关。两个至关重要的发育过程,即生殖细胞分化和早期胚胎发生,提供了实验上可及的模型,试图揭示APs难以捉摸的功能。