A heparin-binding growth factor, midkine, binds to a chondroitin sulfate proteoglycan, PG-M/versican.

A heparin-binding growth factor, midkine, binds to a chondroitin sulfate proteoglycan, PG-M/versican.
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肝素结合生长因子中期因子与硫酸软骨素蛋白聚糖 PG-M/versican 结合。

DOI:
10.1046/j.1432-1327.2000.01440.x
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发表时间:
2000
期刊:
European journal of biochemistry
影响因子:
--
通讯作者:
T. Muramatsu
T. Muramatsu
中科院分区:
--
文献类型:
--
作者:
K. Zou;H. Muramatsu;S. Ikematsu;S. Sakuma;R. Salama;T. Shinomura;K. Kimata;T. Muramatsu

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中期因子是一种肝素结合生长因子,具有促进存活和增强迁移的活性。为了了解中期因子信号转导的调节,我们从13天的小鼠胚胎中分离出中期因子结合蛋白聚糖,此时中期因子强烈表达。去糖基化,然后SDS/PAGE显示各种蛋白质条带;通过凝胶内胰蛋白酶消化和对所得肽进行测序,将其中之一鉴定为PG-M/多功能蛋白聚糖。从第13天小鼠胚胎中分离的PG-M/versican与中期因子结合,Kd为1.0 nM。多效生长因子/肝素结合生长相关分子,其具有与中期因子相关的结构,也被类似地结合。用软骨素酶ABC、AC-I或B消化可消除与中期因子的结合。肝素以及硫酸软骨素D和E抑制结合。在软骨素酶ABC消化后,结合中期因子的PG-M/多功能蛋白聚糖释放4-硫酸化、6-硫酸化、2,6-二硫酸化和4,6-二硫酸化的不饱和二糖。这些结果表明,中期因子结合硫酸软骨素链中的多硫酸化结构域与硫酸皮肤素结构的区域。这种蛋白聚糖可以调节中期因子活性,因为与中期因子的结合可以通过将其浓缩到细胞外周来增强中期因子的作用,或者通过与信号传导受体的结合竞争来抑制该作用。
Midkine is a heparin-binding growth factor with survival-promoting and migration-enhancing activities. In order to understand the regulation of midkine signaling, we isolated midkine-binding proteoglycans from day 13 mouse embryos, when midkine is intensely expressed. Deglycosylation followed by SDS/PAGE revealed various protein bands; one of these was identified as PG-M/versican by in gel trypsin digestion and sequencing the resulting peptides. PG-M/versican isolated from day 13 mouse embryos bound midkine with a Kd of 1.0 nM. Pleiotrophin/heparin-binding growth-associated molecule, which has a structure related to midkine, was also bound similarly. Digestion with chondroitinase ABC, AC-I or B abolished the binding to midkine. Heparin as well as chondroitin sulfate D and E inhibited the binding. After chondroitinase ABC digestion, the midkine-binding PG-M/versican released 4-sulfated, 6-sulfated, 2, 6-disulfated and 4,6-disulfated unsaturated disaccharides. These results suggest that midkine binds to a polysulfated domain in the chondroitin sulfate chain with a region of dermatan sulfate structure. This proteoglycan may modulate the midkine activity, as binding to midkine can enhance midkine action by concentrating it to the cell periphery or inhibit the action by competing with the binding to a signaling receptor.
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