A PKC-η/Fyn-Dependent pathway leading to keratinocyte growth arrest and differentiation
A PKC-η/Fyn-Dependent pathway leading to keratinocyte growth arrest and differentiation
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DOI：
10.1016/s1097-2765(00)00110-6
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发表时间：
2000-11-01
期刊：
影响因子：
16
通讯作者：
Dotto, GP
中科院分区：
文献类型：
--
作者：
Cabodi, S;Calautti, E;Dotto, GP
上皮细胞的生长控制与其他类型的细胞有很大的不同。Fyn的激活是角质形成细胞正常分化所必需的。我们报道，Fyn活性的增加本身通过下调EGF受体(EGFR)信号来抑制角质形成细胞的生长，但不抑制真皮成纤维细胞的生长。蛋白激酶C-ETA也参与角质形成细胞的生长/分化控制。我们发现PKC-ETA对角质形成细胞的生长抑制作用主要依赖于Fyn。PKC-ETA活性是Fyn激活的充要条件，PKC-ETA和Fyn是联合存在的，重组PKC-ETA直接激活Fyn。因此，我们的发现揭示了PKC-ETA和FYN之间的直接相互作用，FYN决定了角质形成细胞(上皮)细胞的生长和分化。
Growth control of epithelial cells differs substantially from other cell types. Activation of Fyn, a Src kinase family member, is required for normal keratinocyte differentiation. We report that increased Fyn activity by itself suppresses growth of keratinocytes, but not dermal fibroblasts, through downmodulation of EGF receptor (EGFR) signaling. Protein kinase C-eta has also been implicated in keratinocyte growth/differentiation control. We show that growth suppression of keratinocytes by PKC-eta depends mostly on Fyn. PKC-eta activity is both necessary and sufficient for Fyn activation, PKC-eta and Fyn are found in association, and recombinant PKC-eta directly activates Fyn. Thus, our findings reveal a direct cross talk between PKC-eta and Fyn, which presides over the decision between keratinocyte (epithelial) cell growth and differentiation.