Urokinase receptor expression involves tyrosine phosphorylation of phosphoglycerate kinase.
Urokinase receptor expression involves tyrosine phosphorylation of phosphoglycerate kinase.
复制标题
尿激酶受体表达涉及磷酸甘油酸激酶的酪氨酸磷酸化。
DOI：
10.1007/s11010-009-0273-4
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发表时间：
2010
影响因子：
4.3
通讯作者：
Shetty,Sreerama
中科院分区：
文献类型：
--
作者：
Shetty,Praveenkumar;Velusamy,Thirunavukkarasu;Bhandary,YashodharP;Liu,MingC;Shetty,Sreerama
尿激酶型纤溶酶原激活物（uPA）与其受体uPAR的相互作用在包括癌症在内的一些病理生理过程中起着核心作用。uPA通过稳定uPAR mRNA诱导自身细胞表面受体表达。其机制涉及51 nt uPAR mRNA编码序列与磷酸甘油酸激酶（PGK）结合以下调细胞表面uPAR表达。uPA处理介导的PGK酪氨酸磷酸化增强了uPAR mRNA的稳定性。相反，酪氨酸磷酸化的抑制增加了PGK与uPAR mRNA的结合，并减弱了upa诱导的uPAR表达。对PGK特异肽区的定位表明，其第1-100个氨基酸与uPAR mRNA相互作用。为了确定uPA是否通过激活PGK的酪氨酸残基来调节uPAR的表达，我们对特定的酪氨酸残基进行了突变，并测试了突变PGK干扰uPAR表达的能力。通过突变Y76残基抑制酪氨酸磷酸化可消除uPA处理诱导的uPAR表达。这些发现共同证明，存在于PGK分子第1 / 4的Y76残基参与了肺上皮细胞表面uPAR的表达。该区域可以有效地模拟整个PGK分子抑制肿瘤细胞生长的功能。
The interaction of urokinase-type plasminogen activator (uPA) with its receptor, uPAR, plays a central role in several pathophysiological processes, including cancer. uPA induces its own cell surface receptor expression through stabilization of uPAR mRNA. The mechanism involves binding of a 51 nt uPAR mRNA coding sequence with phosphoglycerate kinase (PGK) to down regulate cell surface uPAR expression. Tyrosine phosphorylation of PGK mediated by uPA treatment enhances uPAR mRNA stabilization. In contrast, inhibition of tyrosine phosphorylation augments PGK binding to uPAR mRNA and attenuates uPA-induced uPAR expression. Mapping the specific peptide region of PGK indicated that its first quarter (amino acids 1–100) interacts with uPAR mRNA. To determine if uPAR expression by uPA is regulated through activation of tyrosine residues of PGK, we mutated the specific tyrosine residue and tested mutant PGK for its ability to interfere with uPAR expression. Inhibition of tyrosine phosphorylation by mutating Y76 residue abolished uPAR expression induced by uPA treatment. These findings collectively demonstrate that Y76 residue present in the first quarter of the PGK molecule is involved in lung epithelial cell surface uPAR expression. This region can effectively mimic the function of a whole PGK molecule in inhibiting tumor cell growth.