The autocrine motility factor (AMF) and AMF-receptor combination needs sugar chain recognition ability and interaction using the C-terminal region of AMF.
The autocrine motility factor (AMF) and AMF-receptor combination needs sugar chain recognition ability and interaction using the C-terminal region of AMF.
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自分泌运动因子 (AMF) 和 AMF-受体组合需要糖链识别能力和利用 AMF C 末端区域的相互作用。
DOI：
10.1016/j.jmb.2006.02.046
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发表时间：
2006
影响因子：
5.6
通讯作者：
Nagase,Hisamitsu
中科院分区：
文献类型：
--
作者：
Haga,Arayo;Tanaka,Nobutada;Funasaka,Tatsuyoshi;Hashimoto,Kazunori;Nakamura,KazuoT;Watanabe,Hideomi;Raz,Avraham;Nagase,Hisamitsu
自分泌运动因子（AMF）促进细胞运动或侵袭，并调节肿瘤血管生成或腹水积聚。这些信号是由AMF与其受体（AMFR）（细胞表面的糖蛋白）之间的结合触发的。AMF已被鉴定为磷酸己糖异构酶（PHI）。先前的报道表明，外消旋-PHI的底物识别对于受体结合是重要的。晶体学研究表明，AMF由三个结构域组成，并且PHI的底物或抑制剂储存在大结构域和小结构域之间，对应于大约残基117-288。在这里，定点突变被用来调查18重组人AMF点突变体涉及关键氨基酸残基的底物或酶抑制剂的识别或结合。与PHI底物的磷酸基团相互作用的残基的突变显著降低了细胞运动刺激活性。它们对AMFR的结合能力也低于野生型人AMF。保留酶活性的突变体显示出运动刺激作用和受体结合，并对PHI抑制剂敏感。缺乏N-糖链的突变体AMFR在细胞膜上表达，但对AMF刺激没有反应，N-糖苷酶处理的AMFR不与AMF的受体结合竞争。此外，含有底物储存结构域和C-末端区域的AMF结构域刺激细胞运动。这些结果表明，AMFR的N-糖侧链是一个触发器，AMF的117-C-末端部分和AMFR的胞外核心蛋白之间的相互作用是需要在AMF-AMFR相互作用。
The autocrine motility factor (AMF) promotes cellular locomotion or invasion, and regulates tumor angiogenesis or ascites accumulation. These signals are triggered by binding between AMF and its receptor (AMFR), a glycoprotein on the cell surface. AMF has been identified as phosphohexose isomerase (PHI). Previous reports have suggested that the substrate-recognition of exo-PHI is significant for receptor binding. Crystallographic studies have shown that AMF consists of three domains, and that the substrate or inhibitor of PHI is stored between the large and small domains, corresponding to approximately residues 117–288. Here, site-directed mutagenesis was used to investigate 18 recombinant human AMF point mutants involving critical amino acid residues for substrate or enzyme inhibitor recognition or binding. Mutation of residues that interact with the phosphate group of the PHI substrate significantly reduced the cell motility-stimulating activity. Their binding capacities for AMFR were also lower than wild-type human AMF. Mutants that retained the enzymic activity showed the motility-stimulating effect and receptor binding and had sensitivity to a PHI inhibitor. Mutant AMFR lacking the N-sugar chain was expressed on the cell membrane but did not respond to AMF-stimulation, and N-glycosidase-treated AMFR did not compete with receptor binding of AMF. Furthermore, the AMF domains that contain the substrate storage domain and C-terminal region stimulate cell locomotion. These results suggest that the N-glyco side-chain of AMFR is a trigger and that interaction between the 117-C-terminal part of AMF and the extracellular core protein of AMFR is needed during AMF–AMFR interactions.
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影响因子：
11.2
作者：
S. Tsutsumi;S. Gupta;V. Hogan;John G. Collard;A. Raz
通讯作者：
S. Tsutsumi;S. Gupta;V. Hogan;John G. Collard;A. Raz
自分泌运动因子刺激人黑色素瘤细胞中三磷酸肌醇增加三倍。
DOI：
--
发表时间：
1990
期刊：
Biochemical and Biophysical Research Communications - BBRC
影响因子：
--
作者：
E. Kohn;L. Liotta;E. Schiffmann
通讯作者：
E. Schiffmann
细胞形状调节改变转移性黑色素瘤细胞表面抗原的糖基化
影响因子：
6.4
作者：
I. Nabi;A. Raz
通讯作者：
A. Raz
通过晶体结构分析和定点诱变研究检查人自分泌运动因子细胞因子活性的抑制机制。
DOI：
10.1016/s0022-2836(02)00186-9
发表时间：
2002
期刊：
Journal of molecular biology.
影响因子：
--
作者：
Tanaka,Nobutada;Haga,Arayo;Uemura,Hiroshi;Akiyama,Hiroko;Funasaka,Tatsuyoshi;Nagase,Hisamitsu;Raz,Avraham;Nakamura,KazuoT
通讯作者：
Nakamura,KazuoT
嗜热脂肪芽孢杆菌6-磷酸葡萄糖异构酶保守阳离子残基的突变分析。
DOI：
10.1046/j.1432-1327.1998.2570500.x
发表时间：
1998
期刊：
European journal of biochemistry
影响因子：
--
作者：
M. Meng;Y. Chen;Y. Hsiao;Y. Itoh;M. Bagdasarian
通讯作者：
M. Bagdasarian