MKK6 increases the melanocyte dendricity through the regulation of Rho family GTPases.
BACKGROUND
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.


OBJECTIVE
The aim of this study is to investigate and explore the involvement of p38 MAPK in melanocyte dendrite formation.


METHODS
We transduced melanoma cells with adenovirus harboring the expression cassette for constitutive active form of MKK6, an upstream MAPKK for p38 MAPK.


RESULTS
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.


CONCLUSIONS
These results suggest that MKK6 is an authentic regulator for melanocytes dendricity, through the modulation of Rho family GTPases.
Kim
Mi Yoon
MY
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea.
Choi
Tae-Young
TY
Kim
Jin-Hwa
JH
Lee
Ju Hye
JH
Kim
Jin Gu
JG
Sohn
Kyung-Cheol
KC
Yoon
Kyung-Sup
KS
Kim
Chang Deok
CD
Lee
Jeung-Hoon
JH
Yoon
Tae-Jin
TJ
D045744:Cell Line, Tumor; D003712:Dendrites / Q000648:ultrastructure*; D006801:Humans; D048669:MAP Kinase Kinase 6 / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D048669:MAP Kinase Kinase 6; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein