title: MKK6 increases the melanocyte dendricity through the regulation of Rho family GTPases.
abstract: 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.
authors.affiliation: Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea.
authors.forename: Mi Yoon
authors.initials: MY
authors.lastname: Kim
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Choi
authors.forename: Jin-Hwa
authors.initials: JH
authors.lastname: Kim
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Lee
authors.forename: Jin Gu
authors.initials: JG
authors.lastname: Kim
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.forename: Kyung-Sup
authors.initials: KS
authors.lastname: Yoon
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Yoon
mesh_terms: 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
chemical_list: 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