KINASE-ACTIVITY CONTROLS THE SORTING OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR WITHIN THE MULTIVESICULAR BODY
KINASE-ACTIVITY CONTROLS THE SORTING OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR WITHIN THE MULTIVESICULAR BODY
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DOI：
10.1016/0092-8674(90)90474-s
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发表时间：
1990-05-18
期刊：
影响因子：
64.5
通讯作者：
HOPKINS, CR
中科院分区：
文献类型：
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作者：
FELDER, S;MILLER, K;HOPKINS, CR
我们比较了在缺乏内源性受体的NIH3T3细胞中分别表达的表皮生长因子受体(EGF-R)和点突变的EGF-R的内化和细胞内分选。两种EGF受体都能迅速内化，但只有莫能菌素或在20℃时才能下调KR的表面表达。此外，突变受体单独内化的EGF有很大比例未降解地返回到细胞表面。因此，与野生型受体不同，激酶阴性的EGF-R可以循环使用。在电子显微镜下，这两种受体早期的内吞途径是相同的，但在10-20分钟后，途径在多泡小体(MVB)处发生了分歧。野生型EGF-R定位于内囊泡，定位于内囊泡，而非激活型EGF-R定位于MBV的表膜，定位于小的小管泡。我们得出结论，循环降解的内化受体的分选可以通过MBV内的空间分离发生，而EGF-R的分选受酪氨酸激酶活性控制。
We compared the internalization and intracellular sorting of epidermal growth factor receptor (EGF-R) and point mutant kinase-negative EGF-R separately expressed in NIH 3T3 cells lacking endogenous receptor. Both EGF-Rs internalized rapidly, but kinase-negative receptor was surface down-regulated only with monensin or at 20.degree.C. Furthermore, EGF internalized by mutant receptor alone was, in significant proportion, returned to the cell surface undegraded. Hence, unlike wild-type receptor, kinase-negative EGF-R recycles. By electron microscopy the early pathways of endocytosis for the two receptors were identical; however, after 10-20 min the pathways diverged at the multivesicular body (MVB). Wild-type EGF-R, destined for degradation, localized to internal vesicles, while kinase-negative EGF-R, destined for recycling, localized to surface membranes of the MBVs and moved to small tubulovesicles. We conclude that sorting of internalized receptor for degradation of recycling can occur through spatial segregation within the MBV, and sorting of EGF-R is controlled by tyrosine kinase activity.