ArticleMolecular cell2022
Lyso-PAF, a biologically inactive phospholipid, contributes to RAF1 activation.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Suppressing neural stem cell PLA2G7 restores inhibitory circuit function and improves cognition in aging mice.Nature aging · 2026Article
- Potential Mechanisms of Platelet Dysfunction and Bleeding in Acid Sphingomyelinase Deficiency.Cells · 2026Review
- Pla2g7 regulates bone homeostasis via Alox12/12-HETE/Gpr31 signaling axis.Nature communications · 2025Article
- Secondary accumulation of lyso-platelet activating factors in lysosomal storage diseases.Molecular genetics and metabolism · 2025Article
- GADD45G operates as a pathological sensor orchestrating reactive gliosis and neurodegeneration.Neuron · 2025Article
- TNFα activation of the PLEKHA5-FCRLA axis disturbs lipid metabolism, leading to the progression of cutaneous malignant melanoma.Lipids in health and disease · 2025Article
- The expression of congenital Shoc2 variants induces AKT-dependent crosstalk activation of the ERK1/2 pathway.Human molecular genetics · 2024Article
- Dietary supplementation withAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- The effect of stir-frying on the aging of oat flour during storage: A study based on lipidomics.Food science & nutrition · 2024Article
- NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth.Molecular cancer research : MCR · 2024Article
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Authors and funding
14 authors.
Funding
Abstract
Phospholipase A2, group VII (PLA2G7) is widely recognized as a secreted, lipoprotein-associated PLA2 in plasma that converts phospholipid platelet-activating factor (PAF) to a biologically inactive product Lyso-PAF during inflammatory response. We report that intracellular PLA2G7 is selectively important for cell proliferation and tumor growth potential of melanoma cells expressing mutant NRAS, but not cells expressing BRAF V600E. Mechanistically, PLA2G7 signals through its product Lyso-PAF to contribute to RAF1 activation by mutant NRAS, which is bypassed by BRAF V600E. Intracellular Lyso-PAF promotes p21-activated kinase 2 (PAK2) activation by binding to its catalytic domain and altering ATP kinetics, while PAK2 significantly contributes to S338-phosphorylation of RAF1 in addition to PAK1. Furthermore, the PLA2G7-PAK2 axis is also required for full activation of RAF1 in cells stimulated by epidermal growth factor (EGF) or cancer cells expressing mutant KRAS. Thus, PLA2G7 and Lyso-PAF exhibit intracellular signaling functions as key elements of RAS-RAF1 signaling.
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