Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor is a multifunctional phosphoprotein
Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor is a multifunctional phosphoprotein
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DOI：
10.1016/s0167-4838(00)00075-3
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发表时间：
2000-07-14
期刊：
影响因子：
--
通讯作者：
Raz, A
中科院分区：
文献类型：
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作者：
Haga, A;Niinaka, Y;Raz, A
磷酸己糖异构酶（Phosphohexose isomerase，PHI）是胞外酶家族的一员，在糖酵解和糖异生途径中起着关键作用。在分泌后，PHI作为细胞因子与肿瘤自分泌运动因子（AMF）、神经白细胞介素（NLK）和成熟因子（MF）一起起作用。信号传导通过其与细胞表面78 kDa糖蛋白（gp 78）结合而启动。然而，由于PHI蛋白是通过非经典途径从细胞释放的“无前导”分泌蛋白，我们质疑该分子是否经历翻译后修饰，同时保留适当的折叠并保持完整的酶促和运动活性。为了解决这个问题，我们已经产生，表达和分离的重组人AMF（rhAMF）。rhAMF保留了天然AMF的生物活性，即，催化磷酸己糖异构化并刺激细胞运动。此外，我们在这里显示，人的PHI是磷酸化的丝氨酸185酪蛋白激酶II（CK II），我们提供的实验证据表明，这种磷酸化与分泌，从而阐明细胞内信号传递的细胞响应AMF/NLK/MF的刺激提供见解。(C)2000 Elsevier Science B. V.保留所有权利。
Phosphohexose isomerase (PHI) is a member of the ectoenzyme/exoenzyme family and plays a key role in both glycolysis and gluconeogenesis pathways. Upon secretion PHI acts as a cytokine with tumor autocrine motility factor (AMF), neuroleukin (NLK) and maturation factor (MF) functions. Signaling is initiated by its binding to a cell surface 78 kDa glycoprotein (gp78). However, since PHI protein is a 'leaderless' secretory protein, released from cells via a non-classical route(s), we questioned whether the molecule undergoes post-translation modification while retaining proper folding and maintaining intact enzymatic and motogenic activities. To address this, we have generated, expressed and isolated a recombinant human AMF (rhAMF). The rhAMF retained the biological activities of the native AMF, i.e., catalyzes phosphohexose isomerization and stimulated cell motility. Additionally, we show here that human PHI is phosphorylated at serine 185 by casein kinase II (CK II) and we provide experimental evidence suggesting that this phosphorylation is associated with secretion, thus providing insights for elucidating the intracellular signal transmission of cell response to stimulation by AMF/NLK/MF. (C) 2000 Elsevier Science B.V. All rights reserved.