PURIFICATION OF A HUMAN-MILK PROTEIN CLOSELY SIMILAR TO TUMOR-SECRETED PHOSPHOPROTEINS AND OSTEOPONTIN
PURIFICATION OF A HUMAN-MILK PROTEIN CLOSELY SIMILAR TO TUMOR-SECRETED PHOSPHOPROTEINS AND OSTEOPONTIN
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DOI：
10.1016/0167-4838(89)90092-7
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发表时间：
1989-06-13
期刊：
影响因子：
--
通讯作者：
TENEN, DG
中科院分区：
文献类型：
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作者：
SENGER, DR;PERRUZZI, CA;TENEN, DG
多种啮齿动物和人肿瘤细胞分泌分子量（Mr）为7558000（仓鼠）、62000（大鼠、小鼠）、67000（人）的抗原相关磷蛋白（Senger，D.R.和Perruzzi，C.A.（1985）Cancer Res.45，5818-5823）。这些磷蛋白的表达与转化有关;肿瘤细胞产生的这种蛋白质至少是正常或未转化细胞的10倍或更多。源自大鼠肿瘤分泌的磷蛋白的N-末端和内部序列表明其与大鼠骨桥蛋白相同，骨桥蛋白是一种具有Arg-Gly-Asp细胞结合序列的骨蛋白（Oldberg，A.，Frazen，A. Heingegard，D.等人（1986）Proc. Acad. Sci. USA 83，8819-8823）。针对Mr 62000大鼠肿瘤分泌的磷蛋白的抗体被发现与人乳中Mr 75000和Mr 35000的成分结合，表明乳汁中含有抗原相关蛋白。以3 - 10 μ g/ml的浓度存在于人乳中的Mr 75000蛋白已被纯化至均一。Mr 35000组分显然是通过蛋白水解裂解从Mr 75000蛋白衍生而来的，并且这种裂解在凝血酶存在下也在体外发生。N-末端和内部氨基酸序列来自Mr 75000牛奶蛋白，并发现类似（12/21残基）的N-末端和内部序列来自大鼠肿瘤分泌的磷蛋白和骨桥蛋白。此外，来源于人乳蛋白的N-末端的序列与人骨唾液酸蛋白I（大鼠骨桥蛋白的可能的人同系物）的序列相同（Fisher，L.W.，G.R.霍金斯图罗斯，北和Termine，J.D.（1987）J. Biol. Chem. 262. 9702-9708）。
A wide variety of rodent and human tumor cells secrete antigenically related phosphoproteins with molecular weights (Mr) of 7s 58000 (hamster), 62000 (rat, mouse), 67000 (human (Senger, D.R. and Perruzzi, C.A. (1985) Cancer Res. 45, 5818-5823). Expression of these phosphoproteins is transformaiton-related; tumor cells produced at least 10-fold or more of this protein as compared to their normal or untransformed counterparts. N-terminal and internal sequences derived from the rat tumor-secreted phosphoprotein indicate that it is identical to rat osteopontin, a bone protein with an Arg-Gly-Asp cell-binding sequence (Oldberg, A., Frazen, A. and Heingegard, D. (1986) Proc. Natl. Acad. Sci. USA 83, 8819-8823). Antibody raised to the Mr 62000 rat tumor-secreted phosphoprotein was found to bind Mr 75000 and Mr 35000 components of human milk, inicating that milk contains antigencially related proteins. The Mr 75000 protein, which is present in human milk at concentrations ranging from 3 to 10 .mu.g/ml, has been purified to homogeneity. The Mr35000 component is apparently derived from the Mr 75000 protein byproteolytic cleavage, and this cleavage also occurs in vitro in the presence of thrombin. N-terminal and internal amino acid sequences were derived from Mr 75000 milk protein and found to be similar (12/21 residues) to N-terminal and internal sequences derived from the rat tumor-secreted phosphoprotein and osteopontin. Moreover, sequence derived from the N-terminus of the human milk protein is identical to that of human bone sialoprotein I (the likely human homolog ofrat osteopontin) (Fisher, L.W., Hawkins, G.R., Tuross, N. and Termine, J.D. (1987) J. Biol. Chem. 262. 9702-9708).