Characterization and Developmental Regulation of Proteoglycan-Type Protein Tyrosine Phosphatase ζ/RPTP β Isoforms
Characterization and Developmental Regulation of Proteoglycan-Type Protein Tyrosine Phosphatase ζ/RPTP β Isoforms
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蛋白多糖型蛋白酪氨酸磷酸酶 ζ/RPTP β 异构体的表征和发育调控
DOI：
10.1093/oxfordjournals.jbchem.a021959
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发表时间：
1998
影响因子：
2.7
通讯作者：
M. Noda
中科院分区：
文献类型：
--
作者：
T. Nishiwaki;N. Maeda;M. Noda
蛋白酪氨酸磷酸酶zeta （PTPzeta/RPTPbeta）是一种特异性表达于大脑的受体样蛋白酪氨酸磷酸酶。选择性剪接产生该分子的三种同工异构体：PTPzeta- a， PTPzeta的全长形式；PTPzeta- b， PTPzeta的简称；以及细胞外变体PTPzeta-S。在这里，我们确定了所有这些亚型，包括PTPzeta-B，作为硫酸软骨素蛋白聚糖，并表征了它们的碳水化合物修饰和在大鼠大脑中的表达谱。PTPzeta-A的表达水平在产前维持，出生后迅速下降。PTPzeta-S以类似的方式表达，尽管出生后逐渐减少。相比之下，从胚胎第13天（E13）到成年期，PTPzeta-B的含量相对恒定。PTPzeta-A和-S在发育过程中只以蛋白聚糖的形式持续表达，但在E13-15时，PTPzeta-B以非蛋白聚糖的形式被检测到。此外，PTPzeta-B不含LeX、HNK-1碳水化合物或硫酸角蛋白，尽管PTPzeta-A和-S通常被这些碳水化合物修饰。转染PTPzeta-A和-B cdna的L细胞将这些蛋白表达为具有酶活性的硫酸软骨素蛋白聚糖。在免疫荧光显微镜下，L细胞中的PTPzeta-A和-B在细胞皮层结构中显示出基本相似的定位，尽管PTPzeta-A的未成熟或加工形式在细胞内斑块结构中累加积累。这些结果表明，PTPzeta的三种亚型在发育过程中受到不同的调控，并且PTPzeta- b的胞外缺失区对碳水化合物修饰的测定很重要。
Protein tyrosine phosphatase zeta (PTPzeta/RPTPbeta) is a receptor-like protein tyrosine phosphatase specifically expressed in the brain. Alternative splicing produces three isoforms of this molecule: PTPzeta-A, the full-length form of PTPzeta; PTPzeta-B, the short form of PTPzeta; and PTPzeta-S, an extracellular variant. Here, we identified all these isoforms, including PTPzeta-B, as chondroitin sulfate proteoglycans, and characterized their carbohydrate modification and expression profiles in the rat brain. The level of PTPzeta-A expression was maintained during the prenatal period and decreased rapidly after birth. PTPzeta-S was expressed in a similar manner, although the postnatal decrease was gradual. In contrast, relatively constant amounts of PTPzeta-B were observed from embryonic day 13 (E13) through adulthood. PTPzeta-A and -S were constantly expressed only as proteoglycans during development, but a substantial amount of PTPzeta-B was detected in a non-proteoglycan form at E13-15. Moreover, PTPzeta-B did not contain LeX, HNK-1 carbohydrate, or keratan sulfate, although PTPzeta-A and -S were generally modified with these carbohydrates. L cells transfected with PTPzeta-A and -B cDNAs expressed these proteins as enzymatically active chondroitin sulfate proteoglycans. The PTPzeta-A and -B in L cells showed essentially similar localizations in cell cortical structures on immunofluorescence microscopy, although immature or processed forms of PTPzeta-A were accumulated additively in intracellular patchy structures. These results show that the three isoforms of PTPzeta are differentially regulated during development, and that the extracellular deleted region in PTPzeta-B is important for determination of carbohydrate modification.