Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea.
J Dermatol Sci. 2010 Nov;60(2):114-9. doi: 10.1016/j.jdermsci.2010.08.006. Epub 2010 Sep 24.
Melanocyte dendrites serve as the principal conduit for melanosome transfer. The dendrite formation requires actin polymerization mediated by Rho family GTPases including RhoA, Rac1 and Cdc42.
The aim of this study is to investigate and explore the involvement of p38 MAPK in melanocyte dendrite formation.
We transduced melanoma cells with adenovirus harboring the expression cassette for constitutive active form of MKK6, an upstream MAPKK for p38 MAPK.
We investigated the effect of melanogenic inducers on melanocyte dendricity, using SK-mel-24 melanoma cells because that this cell line is refractory to several melanogenic inducers in terms of melanogenesis. TPA-induced the phosphorylation of p38 MAPK and the elongation of dendrite length, suggesting that MKK6 may be involved in this process. Overexpression of the constitutive active form of MKK6 resulted in significant elongation of dendrites in the melanoma cell line SK-mel-24. Moreover, overexpression of MKK6 ultimately led to the upregulation of Cdc42 and Rac1, suggesting that MKK6 acts as a crucial upstream signaling molecule for Rho family GTPases. When overexpressed in normal human epidermal melanocytes, MKK6 led also the increase of dendrite length.
These results suggest that MKK6 is an authentic regulator for melanocytes dendricity, through the modulation of Rho family GTPases.
黑素细胞树突作为黑素体转移的主要通道。树突的形成需要 Rho 家族 GTP 酶（包括 RhoA、Rac1 和 Cdc42）介导的肌动蛋白聚合。
本研究旨在探讨 p38MAPK 在黑素细胞树突形成中的作用。
我们用携带组成型激活型 MKK6 表达盒的腺病毒转染黑素瘤细胞，MKK6 是 p38MAPK 的上游 MAPKK。
我们研究了黑素生成诱导剂对黑素细胞树突状的影响，使用 SK-mel-24 黑素瘤细胞，因为该细胞系在黑素生成方面对几种黑素生成诱导剂有抗性。TPA 诱导 p38MAPK 的磷酸化和树突长度的伸长，表明 MKK6 可能参与了这一过程。组成型激活型 MKK6 的过表达导致 SK-mel-24 黑素瘤细胞系树突的显著伸长。此外，MKK6 的过表达最终导致 Cdc42 和 Rac1 的上调，表明 MKK6 作为 Rho 家族 GTP 酶的关键上游信号分子发挥作用。当在正常人表皮黑素细胞中过表达时，MKK6 也导致树突长度的增加。
这些结果表明，MKK6 通过调节 Rho 家族 GTP 酶，是黑素细胞树突状的真正调节剂。
