Cutting edge: Internalization of transduced E-selectin by cultured human endothelial cells: Comparison of dermal microvascular and umbilical vein cells and identification of a phosphoserine-type di-leucine motif
Cutting edge: Internalization of transduced E-selectin by cultured human endothelial cells: Comparison of dermal microvascular and umbilical vein cells and identification of a phosphoserine-type di-leucine motif
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DOI：
10.4049/jimmunol.168.5.2091
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发表时间：
2002-03-01
影响因子：
4.4
通讯作者：
Pober, JS
中科院分区：
文献类型：
--
作者：
Kluger, MS;Shiao, SL;Pober, JS
人真皮微血管内皮细胞（HDMEC）上持续表达E-选择素，被认为介导皮肤特异性T细胞归巢，是细胞因子诱导后表面蛋白内化速率缓慢的结果。用E-选择素cDNA转导未活化的HDMEC后，内化率在很大程度上不依赖于表面蛋白表达水平的增加，导致超过4小时的t（1/2）值延长，与细胞因子诱导后观察到的相当。在HUVEC中，内化速率随着表面表达水平的增加而增加，导致t（1/2）基本恒定，小于2 h。因此，内化过程，而不是细胞因子的反应性或E-选择素结构的差异，在内皮细胞的行为。细胞质区域的突变分析证明了涉及I588和L589的双亮氨酸型基序的作用，但不包括推定的酪氨酸型基序。E-选择素表面表达的控制似乎是磷酸丝氨酸依赖性的，因为丙氨酸而不是天冬氨酸取代S581减缓E-选择素内化。
Persistent E-selectin expression on human dermal microvascular endothelial cells (HDMEC), believed to mediate skin-specific T cell homing, results from a slow rate of surface protein internalization after cytokine induction. Following transduction of unactivated HDMEC with E-selectin cDNA, the rate of internalization was largely independent of increasing levels of surface protein expression, leading to prolonged t(1/2) values of over 4 h, comparable to that observed following cytokine induction. In HUVEC, the rate of internalization increased with surface expression level, leading to an essentially constant t(1/2) of under 2 h. Thus, the internalization process rather than cytokine responsiveness or E-selectin structure underlies the difference in endothelial cell behavior. Mutational analysis of the cytoplasmic region demonstrated a role for a di-leucine-type motif involving I588 and L589 but not for a putative tyrosine-type motif. Control of E-selectin surface expression appears to be phosphoserine dependent, since alanine but not aspartic acid substitution for S581 slows E-selectin internalization.