- [Experimental & Molecular Medicine] PAK4 phosphorylates cyclin-dependent kinase 2 to promote the G1S transition during adipogene
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- 2025-10-20 15:12:09|
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- 2025-10-20 15:12:09|
[Title]
PAK4 phosphorylates cyclin-dependent kinase 2 to promote the G1S transition during adipogenesis
[Corresponding Author]
* Byung-Hyun Park(bhparkut@kaist.ac.kr)
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
* Eun Ju Bae(ejbae7@jbnu.ac.kr)
- School of Pharmacy and Institute of New Drug Development, Jeonbuk National University, Jeonju, Republic of Korea.
* Yoonji Lee(yoonjilee@cau.ac.kr)
- College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
[Journal]
Experimental & Molecular Medicine (2025) 57:2121–2132; https://doi.org/10.1038/s12276-025-01525-x
[Abstract]p21-activated kinase 4 (PAK4), a member of the PAK family (PAK1–6), was initially recognized for its role in tumor development.
Recently, we discovered PAK4’s involvement in triacylglycerol lipolysis in adipocytes. However, its function in adipogenesis remains
unclear. Here we show that PAK4 plays a critical role in adipocyte differentiation. Following adipogenic stimulation, PAK4 protein
levels increased. Knockdown of PAK4 in 3T3-L1 preadipocytes or human stromal vascular cells, as well as pharmacological inhibition
of PAK4 in 3T3-L1 cells, impaired adipogenesis, as indicated by reduced expression of adipocyte marker genes and decreased lipid
accumulation. Mechanistically, PAK4 phosphorylated cyclin-dependent kinase 2 at serine 106, a critical step for CCAAT/enhancerbinding
protein β expression during mitotic clonal expansion. Consistent with these findings, preadipocyte-specific Pak4-knockout
mice exhibited reduced fat mass and smaller adipocytes. These results reveal PAK4 as a crucial regulator of adipogenesis and,
together with its inhibitory role in triacylglycerol lipolysis, further underscore its potential as a therapeutic target for obesity
treatment.
PAK4 phosphorylates cyclin-dependent kinase 2 to promote the G1S transition during adipogenesis
[Corresponding Author]
* Byung-Hyun Park(bhparkut@kaist.ac.kr)
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
* Eun Ju Bae(ejbae7@jbnu.ac.kr)
- School of Pharmacy and Institute of New Drug Development, Jeonbuk National University, Jeonju, Republic of Korea.
* Yoonji Lee(yoonjilee@cau.ac.kr)
- College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
[Journal]
Experimental & Molecular Medicine (2025) 57:2121–2132; https://doi.org/10.1038/s12276-025-01525-x
[Abstract]
Recently, we discovered PAK4’s involvement in triacylglycerol lipolysis in adipocytes. However, its function in adipogenesis remains
unclear. Here we show that PAK4 plays a critical role in adipocyte differentiation. Following adipogenic stimulation, PAK4 protein
levels increased. Knockdown of PAK4 in 3T3-L1 preadipocytes or human stromal vascular cells, as well as pharmacological inhibition
of PAK4 in 3T3-L1 cells, impaired adipogenesis, as indicated by reduced expression of adipocyte marker genes and decreased lipid
accumulation. Mechanistically, PAK4 phosphorylated cyclin-dependent kinase 2 at serine 106, a critical step for CCAAT/enhancerbinding
protein β expression during mitotic clonal expansion. Consistent with these findings, preadipocyte-specific Pak4-knockout
mice exhibited reduced fat mass and smaller adipocytes. These results reveal PAK4 as a crucial regulator of adipogenesis and,
together with its inhibitory role in triacylglycerol lipolysis, further underscore its potential as a therapeutic target for obesity
treatment.
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