Cabodi S, Calautti E, Talora C, Kuroki T, Stein P L, Dotto G P
Cutaneous Biology Research Center Harvard Medical School and Massachusetts General Hospital, Charlestown, MA 02129, USA.
Mol Cell. 2000 Nov;6(5):1121-9. doi: 10.1016/s1097-2765(00)00110-6.
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.
上皮细胞的生长调控与其他细胞类型有很大不同。Src激酶家族成员Fyn的激活是角质形成细胞正常分化所必需的。我们报告称，Fyn活性的增加本身会通过下调表皮生长因子受体（EGFR）信号传导来抑制角质形成细胞的生长，但不会抑制真皮成纤维细胞的生长。蛋白激酶C-η也与角质形成细胞的生长/分化调控有关。我们表明，PKC-η对角质形成细胞的生长抑制主要依赖于Fyn。PKC-η活性对于Fyn激活既必要又充分，PKC-η和Fyn相互关联，并且重组PKC-η可直接激活Fyn。因此，我们的研究结果揭示了PKC-η和Fyn之间的直接相互作用，它决定了角质形成细胞（上皮）的生长和分化。
