title: Phosphorylation of Bad at Thr-201 by JNK1 promotes glycolysis through activation of phosphofructokinase-1.
abstract: The mitogen-activated protein kinase JNK1 suppresses interleukin-3 withdrawal-induced cell death through phosphorylation of the BH3-only pro-apoptotic Bcl-2 family protein Bad at Thr-201. It is unknown whether JNK1 regulates glycolysis, an important metabolic process that is involved in cell survival, and if so, whether the regulation depends on Thr-201 phosphorylation of Bad. Here we report that phosphorylation of Bad by JNK1 is required for glycolysis through activation of phosphofructokinase-1 (PFK-1), one of the key enzymes that catalyze glycolysis. Genetic disruption of Jnk1 alleles or silencing of Jnk1 by small interfering RNA abrogates glycolysis induced by growth/survival factors such as serum or interleukin-3. Proteomic analysis identifies PFK-1 as a novel Bad-associated protein. Although the interaction between PFK-1 and Bad is independent of JNK1, Thr-201 phosphorylation of Bad by JNK1 is required for PFK-1 activation. Thus, our results provide a novel molecular mechanism by which JNK1 promotes glycolysis for cell survival.
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Deng
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Jianqun
authors.initials: J
authors.lastname: Chen
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jialing
authors.initials: J
authors.lastname: Xiang
authors.forename: Anning
authors.initials: A
authors.lastname: Lin
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D020868:Gene Silencing; D006019:Glycolysis; D007377:Interleukin-3 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods; D013912:Threonine / Q000737:chemistry*; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: D007377:Interleukin-3; D051025:bcl-Associated Death Protein; D013912:Threonine; D010732:Phosphofructokinase-1; D048055:Mitogen-Activated Protein Kinase 8