Human EGF receptor (HER) family and heregulin members are differentially expressed in epidermal keratinocytes and modulate differentiation
Human EGF receptor (HER) family and heregulin members are differentially expressed in epidermal keratinocytes and modulate differentiation
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DOI：
10.1006/excr.2001.5390
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发表时间：
2001-12-10
影响因子：
3.7
通讯作者：
Pittelkow, MR
中科院分区：
文献类型：
--
作者：
De Potter, IY;Poumay, Y;Pittelkow, MR
人表皮生长因子受体(HER)，又名HER1，是一种可激活的酪氨酸激酶受体。HER1激活调节表皮角质形成细胞的生长和分化。在自分泌条件下培养的人角质形成细胞中，研究了HER家族其他成员的表达。HER2和HER3在诱导表皮分化的同时，通过融合表达和上调。角质形成细胞不表达HER4。在融合的角质形成细胞中观察到同源配体hereglin的最高表达，并且hereglinα和β亚型的表达随着融合的进行而下调。重组HER2异构体对角质形成细胞的集落形成和增殖无影响，但HER2和HERS在融合分化角质形成细胞培养中激活HER2和HERS的酪氨酸磷酸化，而对HER1无影响。此外，在这些条件下，Hereglin beta增加了HER2/HER3的异二聚化。HERGβ处理融合培养物与细胞信号和抑制表皮分化有关。HER2、HER-3和HERG共同构成了一个潜在的自分泌-旁分泌系统，参与了表皮的动态平衡和修复，以及参与了过度增殖的病理过程。(C)2001年爱思唯尔科学公司。
Human EGF receptor (HER), also designated HER1, is an activatable tyrosine kinase receptor. HER1 activation regulates cell growth and differentiation in epidermal keratinocytes. Expression of other HER family members was investigated in human keratinocytes cultured under autocrine conditions. HER2 and HER3 are expressed and upregulated by confluence, concurrent with induction of epidermal differentiation. HER4 is not expressed by keratinocytes. Maximum expression of the cognate ligand, heregulin, is observed in subconfluent keratinocytes, and the expression of both heregulin alpha and beta isoforms is downregulated with confluence. Recombinant heregulin isoforms have no effect on colony formation and keratinocyte proliferation, but heregulin beta activates tyrosine phosphorylation of HER2 and HERS, with no effect on HER1, in confluent differentiating keratinocyte cultures. Also, heregulin beta increases HER2/HER3 heterodimerization under those conditions. Treatment of confluent cultures by heregulin beta correlates with cell signaling and inhibition of epidermal differentiation. Together, HER2, HER-3, and heregulin constitute a potential autocrine-paracrine system involved in epidermal homeostasis and repair, as well as in hyperproliferative pathologies. (C) 2001 Elsevier Science.