A tyrosine residue in the juxtamembrane segment of the platelet-derived growth factor beta-receptor is critical for ligand-mediated endocytosis.
A tyrosine residue in the juxtamembrane segment of the platelet-derived growth factor beta-receptor is critical for ligand-mediated endocytosis.
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血小板衍生生长因子β受体近膜片段中的酪氨酸残基对于配体介导的内吞作用至关重要。
DOI：
10.1016/s0021-9258(17)37632-9
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
C. Heldin
中科院分区：
文献类型：
--
作者：
S. Mori;L. Rönnstrand;L. Claesson;C. Heldin
利用一系列酪氨酸残基突变的β受体分析了酪氨酸残基在配体介导的血小板衍生生长因子β受体内吞作用中的重要性，这些突变的β受体共同覆盖了膜旁片段、激酶插入物和羧基末端尾部的所有酪氨酸残基，并检测了激酶域第一和第二部分中的某些酪氨酸残基。在所有这些酪氨酸残基中，似乎只有Tyr-579对内化很重要，因为该残基的突变导致配体诱导的受体内化速度显著降低(约为野生型水平的60%)。用芳香族(Phe)或非芳香族(Asp)残基替换Tyr-579会在相同程度上降低突变受体的内化效率，这表明Tyr-579在β受体中的作用不同于先前描述的基于酪氨酸的内化基序，这些基序最初是为低密度脂蛋白受体确定的。已发现Tyr-579是β受体中的一个自动磷酸化位点。此外，酪氨酸酶阴性受体突变体的内化率不会因Tyr-579的额外突变而改变。因此，Tyr-579的磷酸化对于配体诱导的β受体内化很可能是重要的。
The importance of tyrosine residues in ligand-mediated endocytosis of the platelet-derived growth factor beta-receptor was analyzed using a series of tyrosine residue-mutated beta-receptors, which together cover all of the tyrosine residues in the juxtamembrane segment, the kinase insert, and the carboxyl-terminal tail; also certain of the tyrosine residues within the first and second parts of the kinase domain were examined. Of all of these tyrosine residues, only Tyr-579 seemed to be important for internalization, since mutation of this residue resulted in substantial reduction in the rate of ligand-induced receptor internalization (approximately 60% of the wild-type level). Replacement of Tyr-579 by either an aromatic (Phe) or a nonaromatic (Asp) residue reduced the efficiency of the mutant receptors in internalization to the same extent, suggesting that the role of Tyr-579 in the beta-receptor is different from that of the previously described tyrosine-based internalization motifs, which were first determined for the low density lipoprotein receptor. Tyr-579 has been found to be an autophosphorylation site in the beta-receptor. Moreover, the internalization rate of a kinase negative receptor mutant was not altered by the additional mutation of Tyr-579. Thus, it is likely that phosphorylation of Tyr-579 is important for ligand-induced internalization of the beta-receptor.