Src inhibition induces melanogenesis in human G361 cells

Kyung Eun Ku, Nahyun Choi, Sang Ho Oh, Won Serk Kim, Wonhee Suh, Jong Hyuk Sung

Research output: Contribution to journalArticle

Abstract

The Src kinase family (SKF) includes non-receptor tyrosine kinases that interact with many cellular cytosolic, nuclear and membrane proteins, and is involved in the progression of cellular transformation and oncogenic activity. However, there is little to no evidence on the effect of SKF or its inhibitors on melanogenesis. Therefore, the present study investigated whether C-terminal Src kinase inhibition can induce melanogenesis and examined the associated signaling pathways and mRNA expression of melanogenic proteins. First, whether stimulators of melanogenesis, such as ultraviolet B and α-melanocyte-stimulating hormone, can dephosphorylate Src protein was evaluated, and the results revealed that SU6656 and PP2 inhibited the phosphorylation of Src in G361 cells. Src inhibition by these chemical inhibitors induced melanogenesis in G361 cells and upregulated the mRNA expression levels of melanogenesis-associated genes encoding microphthalmia-associated transcription factor, tyrosinase-related protein 1 (TRP1), TRP2, and tyrosinase. In addition, Src inhibition by small interfering RNA induced melanogenesis and upregulated the mRNA expression levels of melanogenesis-associated genes. As the p38 mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate response element binding (CREB) pathways serve key roles in melanogenesis, the present study further examined whether Src mediates melanogenesis via these pathways. As expected, Src inhibition via SU6656 or PP2 administration induced the phosphorylation of p38 or CREB, as determined by western blotting analysis, and increased the levels of phosphorylated p38 or CREB, as determined by immunofluorescence staining. In addition, the induced pigmentation and melanin content of G361 cells by Src inhibitors was significantly inhibited by p38 or CREB inhibitors. Taken together, these data indicate that Src is associated with melanogenesis, and Src inhibition induces melanogenesis via the MAPK and CREB pathways in G361 cells.

Original languageEnglish
Pages (from-to)3061-3070
Number of pages10
JournalMolecular Medicine Reports
Volume19
Issue number4
DOIs
Publication statusPublished - 2019 Apr 1

Fingerprint

Response Elements
Cyclic AMP
Phosphorylation
src-Family Kinases
Messenger RNA
Microphthalmia-Associated Transcription Factor
Melanocyte-Stimulating Hormones
Gene encoding
Monophenol Monooxygenase
Melanins
Nuclear Envelope
Pigmentation
p38 Mitogen-Activated Protein Kinases
Nuclear Proteins
Mitogen-Activated Protein Kinases
Protein-Tyrosine Kinases
Small Interfering RNA
Genes
Fluorescent Antibody Technique
Membrane Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

Cite this

Ku, Kyung Eun ; Choi, Nahyun ; Oh, Sang Ho ; Kim, Won Serk ; Suh, Wonhee ; Sung, Jong Hyuk. / Src inhibition induces melanogenesis in human G361 cells. In: Molecular Medicine Reports. 2019 ; Vol. 19, No. 4. pp. 3061-3070.
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abstract = "The Src kinase family (SKF) includes non-receptor tyrosine kinases that interact with many cellular cytosolic, nuclear and membrane proteins, and is involved in the progression of cellular transformation and oncogenic activity. However, there is little to no evidence on the effect of SKF or its inhibitors on melanogenesis. Therefore, the present study investigated whether C-terminal Src kinase inhibition can induce melanogenesis and examined the associated signaling pathways and mRNA expression of melanogenic proteins. First, whether stimulators of melanogenesis, such as ultraviolet B and α-melanocyte-stimulating hormone, can dephosphorylate Src protein was evaluated, and the results revealed that SU6656 and PP2 inhibited the phosphorylation of Src in G361 cells. Src inhibition by these chemical inhibitors induced melanogenesis in G361 cells and upregulated the mRNA expression levels of melanogenesis-associated genes encoding microphthalmia-associated transcription factor, tyrosinase-related protein 1 (TRP1), TRP2, and tyrosinase. In addition, Src inhibition by small interfering RNA induced melanogenesis and upregulated the mRNA expression levels of melanogenesis-associated genes. As the p38 mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate response element binding (CREB) pathways serve key roles in melanogenesis, the present study further examined whether Src mediates melanogenesis via these pathways. As expected, Src inhibition via SU6656 or PP2 administration induced the phosphorylation of p38 or CREB, as determined by western blotting analysis, and increased the levels of phosphorylated p38 or CREB, as determined by immunofluorescence staining. In addition, the induced pigmentation and melanin content of G361 cells by Src inhibitors was significantly inhibited by p38 or CREB inhibitors. Taken together, these data indicate that Src is associated with melanogenesis, and Src inhibition induces melanogenesis via the MAPK and CREB pathways in G361 cells.",
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Src inhibition induces melanogenesis in human G361 cells. / Ku, Kyung Eun; Choi, Nahyun; Oh, Sang Ho; Kim, Won Serk; Suh, Wonhee; Sung, Jong Hyuk.

In: Molecular Medicine Reports, Vol. 19, No. 4, 01.04.2019, p. 3061-3070.

Research output: Contribution to journalArticle

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