ArticleThe Journal of investigative dermatology2015
p21-activated kinase 4 critically regulates melanogenesis via activation of the CREB/MITF and β-catenin/MITF pathways.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- MITF Is an Essential and Functionally Multifaceted Transcription Factor in Cutaneous Melanoma.Cancers · 2026Review
- Article
- Immunomodulatory functions of growth differentiation factor 15 in skin aging and inflammatory dermatoses.Frontiers in immunology · 2026Review
- Sebum's effect on wound healing and pigmentation in mice.Skin health and disease · 2025Article
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Review
- Molecular mechanisms underlying Tao-Hong-Si-Wu decoction treating hyperpigmentation based on network pharmacology, Mendelian randomization analysis, and experimental verification.Pharmaceutical biology · 2024Article
- CREB Is Critically Implicated in Skin Mast Cell Degranulation Elicited via FcεRI and MRGPRX2.Cells · 2024Article
- Transcriptome analysis of sexual dimorphism in dorsal down coloration in goslings.BMC genomics · 2024Article
- Anhydrous Alum Inhibits α-MSH-Induced Melanogenesis by Down-Regulating MITF via Dual Modulation of CREB and ERK.International journal of molecular sciences · 2023Article
- FermentedMolecules (Basel, Switzerland) · 2023Article
- Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022Review
- Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells.Acta pharmaceutica Sinica. B · 2022Article
- Diarylpropionitrile inhibits melanogenesis via protein kinase A/cAMP-response element-binding protein/microphthalmia-associated transcription factor signaling pathway in α-MSH-stimulated B16F10 melanoma cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- MiR-585-5p impedes gastric cancer proliferation and metastasis by orchestrating the interactions among CREB1, MAPK1 and MITF.Frontiers in immunology · 2022Article
- Attenuation Effect of Radiofrequency Irradiation on UV-B-Induced Skin Pigmentation by Decreasing Melanin Synthesis and through Upregulation of Heat Shock Protein 70.Molecules (Basel, Switzerland) · 2021Article
- cAMP Response Element Binding-Protein- and Phosphorylation-Dependent Regulation of Tyrosine Hydroxylase by PAK4: Implications for Dopamine Replacement Therapy.Molecules and cells · 2021Article
- Expression of phosphorylated p21-activated kinase 4 is associated with aggressive histologic characteristics and poor prognosis in patients with surgically treated renal cell carcinoma.Investigative and clinical urology · 2021Article
- Monodactylous Longitudinal Melanonychia: A Sign of Bowen's Disease in Skin of Color.Skin appendage disorders · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p21-activated kinase 4 (PAK4) regulates a wide range of cellular events, including cytoskeletal remodeling, cell growth, and survival. Our previous study identified PAK4 as a key regulator of cAMP-response element-binding protein (CREB) that acts upstream of microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. We therefore investigated the role of PAK4 in melanogenesis. Melanocytes express both PAK2 and PAK4 isoforms, but only RNA interference knockdown of PAK4 significantly influenced α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in B16 melanoma cells. Consistent with this result, PAK4 inhibition by PF3758309, a potent ATP-competitive inhibitor of PAKs, suppressed not only α-MSH-induced melanogenesis in B16 melanoma and human epithelial melanocyte cells but also UVB-induced melanogenesis in the skin of melanin-possessing hairless mice (HRM-2) in a dose-dependent manner. Inhibition of PAK4 over several days markedly decreased the levels of CREB, MITF, and tyrosinase in both HRM-2 mice and B16 melanoma cells. Moreover, PAK4 knockdown and inhibition suppressed α-MSH-stimulated β-catenin phosphorylation at serine 675 (S675) but enhanced phosphorylation at S33/37, an indicator for ubiquitination-dependent proteolysis. Together, our results provide evidence that PAK4 promotes α-MSH/UVB-induced melanogenesis via the CREB and Wnt/β-catenin signaling pathways and suggest that PAK4 may be a potential therapeutic target in pigmentation disorders.
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