Lyso-PAF, a biologically inactive phospholipid, contributes to RAF1 activation

Xue Gao1,3,4; Yijie Liu1,3,6; Yuancheng Li2,3; Hao Fan1,3,4; Rong Wu1,3,4; Rukang Zhang1,3,4; Brandon Faubert4; Yu-Ying He4; Marc B. Blssonnette4; Siyuan Xia1,3,8; Dong Chen1,3,7; Hui Mao2,3; Titus J. Boggon5; Jing Chen1,3,4,9

2022-06-02

10.1016/j.molcel.2022.03.026

MOLECULAR CELL   影响因子和分区

1097-2765

1097-4164

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 LysoPAF 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.

SCI

英语

NI论文

其他

NIH["CA140515","CA183594","CA174786"]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000822391900007

CELL PRESS

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
2.Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
3.Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
4.Section of Hematology and Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
5.Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
6.Present address: Department of Pathology, Northwestern University, Chicago, IL 60611, USA
7.Present address: Soochow University, Suzhou 215000, China
8.Present address: Department of Human Cell Biology and Genetics, Southern University of Science and Technology School of Medicine, Shenzhen 518055, China
9.Lead contact

Xue Gao,Yijie Liu,Yuancheng Li,et al. Lyso-PAF, a biologically inactive phospholipid, contributes to RAF1 activation[J]. MOLECULAR CELL,2022,82(11):00264-7.

Xue Gao.,Yijie Liu.,Yuancheng Li.,Hao Fan.,Rong Wu.,...&Jing Chen.(2022).Lyso-PAF, a biologically inactive phospholipid, contributes to RAF1 activation.MOLECULAR CELL,82(11),00264-7.

Xue Gao,et al."Lyso-PAF, a biologically inactive phospholipid, contributes to RAF1 activation".MOLECULAR CELL 82.11(2022):00264-7.