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Updated: Apr 19, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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p21-activated kinase 4 critically regulates melanogenesis via activation of the CREB/MITF and β-catenin/MITF pathways

Cheong-Yong Yun1, Soon-Tae You1, Jin-Hwa Kim2

  • 1Department of Biochemistry and Medical Research Center, College of Medicine, Chungbuk National University, Cheongju, Korea.

The Journal of Investigative Dermatology
|January 7, 2015
PubMed

Insights

p21-activated kinase 4 (PAK4) promotes skin pigmentation by regulating key factors like CREB and MITF. Inhibiting PAK4 reduces melanogenesis, suggesting it

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Dermatology

Background:

  • p21-activated kinase 4 (PAK4) is involved in cellular processes.
  • PAK4 regulates cAMP-response element-binding protein (CREB) and microphthalmia-associated transcription factor (MITF).
  • MITF is a master regulator of melanogenesis.

Purpose of the Study:

  • To investigate the role of PAK4 in melanogenesis.
  • To determine if PAK4 inhibition affects α-melanocyte-stimulating hormone (α-MSH) or UVB-induced pigmentation.

Main Methods:

  • Utilized RNA interference (RNAi) to knockdown PAK4 in B16 melanoma cells.
  • Administered PF3758309, a PAK inhibitor, to B16 melanoma cells, human epithelial melanocytes, and hairless mice (HRM-2).
  • Assessed levels of CREB, MITF, tyrosinase, and β-catenin phosphorylation.

Main Results:

  • PAK4 knockdown significantly affected α-MSH-induced melanogenesis.
  • PAK4 inhibition suppressed both α-MSH and UVB-induced melanogenesis in a dose-dependent manner.
  • PAK4 inhibition decreased CREB, MITF, and tyrosinase levels and altered β-catenin phosphorylation.

Conclusions:

  • PAK4 promotes α-MSH/UVB-induced melanogenesis through CREB and Wnt/β-catenin pathways.
  • PAK4 is a potential therapeutic target for pigmentation disorders.

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