PED/PEA-15 interacts with the 67 kD laminin receptor and regulates cell adhesion, migration, proliferation and apoptosis.
PED/PEA-15 interacts with the 67 kD laminin receptor and regulates cell adhesion, migration, proliferation and apoptosis.
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PED/PEA-15与67 KD层粘连蛋白受体相互作用，并调节细胞粘附，迁移，增殖和凋亡。
DOI：
10.1111/j.1582-4934.2011.01411.x
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发表时间：
2012-07
影响因子：
5.3
通讯作者：
Montuori N
中科院分区：
文献类型：
--
作者：
Formisano P;Ragno P;Pesapane A;Alfano D;Alberobello AT;Rea VE;Giusto R;Rossi FW;Beguinot F;Rossi G;Montuori N
糖尿病中富含的磷蛋白/星形胶质细胞中富含的磷蛋白-15 kD（PED/PEA-15）是一种抗凋亡蛋白，其表达在几种人类癌症中增加。除了细胞凋亡，PED/PEA-15还参与其他主要细胞功能的调节，包括细胞粘附、迁移、增殖和葡萄糖代谢。为了进一步了解该蛋白的功能，我们使用PED/PEA-15作为诱饵进行了酵母双杂交筛选，并确定了67 kD高亲和力层粘连蛋白受体（67 LR）作为相互作用伴侣。67 kD层粘连蛋白受体是细胞外基质（ECM）的非整联蛋白细胞表面受体，来源于37 kD细胞溶质前体（37 LRP）的二聚化。67 LR在人类癌症中高度表达，并被广泛认为是转移侵袭性的分子标志物。PED/PEA-15与67 LR的分子相互作用通过在PED/PEA-15转染的HEK-293细胞的裂解物上用重组His-标记的37 LRP进行的下拉实验来证实。此外，分别在PED/PEA-15转染的HEK-293细胞和U-373胶质母细胞瘤细胞中，过表达或内源性PED/PEA-15与67 LR共免疫沉淀。PED/PEA-15过表达显著增加了67 LR介导的HEK-293细胞粘附和迁移到层粘连蛋白，这反过来又决定了PED/PEA-15在Ser-104和Ser-116中的磷酸化，从而使细胞增殖和抗凋亡。PED/PEA-15通过与67 LR相互作用诱导细胞对ECM衍生信号的反应的能力可能对肿瘤细胞在不良微环境中的存活至关重要，从而有利于转移性扩散和定殖。
Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kD (PED/PEA-15) is an anti-apoptotic protein whose expression is increased in several human cancers. In addition to apoptosis, PED/PEA-15 is involved in the regulation of other major cellular functions, including cell adhesion, migration, proliferation and glucose metabolism. To further understand the functions of this protein, we performed a yeast two-hybrid screening using PED/PEA-15 as a bait and identified the 67 kD high-affinity laminin receptor (67LR) as an interacting partner. 67 kD laminin receptor is a non-integrin cell-surface receptor for the extracellular matrix (ECM), derived from the dimerization of a 37 kD cytosolic precursor (37LRP). The 67LR is highly expressed in human cancers and widely recognized as a molecular marker of metastatic aggressiveness. The molecular interaction of PED/PEA-15 with 67LR was confirmed by pull-down experiments with recombinant His-tagged 37LRP on lysates of PED/PEA-15 transfected HEK-293 cells. Further, overexpressed or endogenous PED/PEA-15 was co-immunoprecipitated with 67LR in PED/PEA-15-transfected HEK-293 cells and in U-373 glioblastoma cells, respectively. PED/PEA-15 overexpression significantly increased 67LR-mediated HEK-293 cell adhesion and migration to laminin that, in turn, determined PED/PEA-15 phosphorylation both in Ser-104 and Ser-116, thus enabling cell proliferation and resistance to apoptosis. PED/PEA-15 ability to induce cell responses to ECM-derived signals through interaction with 67LR may be of crucial importance for tumour cell survival in a poor microenvironment, thus favouring the metastatic spread and colonization.
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影响因子：
12.4
作者：
Kaneda, Y;Kaneda, Y;Tanaka, K
通讯作者：
Tanaka, K
影响因子：
3.8
作者：
Chen, F. X.;Qian, Y. R.;Ji, Y. H.
通讯作者：
Ji, Y. H.
影响因子：
8
作者：
Condorelli, G;Vigliotta, G;Beguinot, F
通讯作者：
Beguinot, F
影响因子：
2.9
作者：
GRAF, J;OGLE, RC;KLEINMAN, HK
通讯作者：
KLEINMAN, HK
影响因子：
2.9
作者：
LANDOWSKI, TH;DRATZ, EA;STARKEY, JR
通讯作者：
STARKEY, JR