title: EGFR phosphorylates FAM129B to promote Ras activation.
abstract: Ras GTPase-activating proteins (GAPs) are important regulators for Ras activation, which is instrumental in tumor development. However, the mechanism underlying this regulation remains elusive. We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-RasGAP to Ras. FAM129B phosphorylation promoted Ras activation, increasing ERK1/2- and PKM2-dependent β-catenin transactivation and leading to the enhanced glycolytic gene expression and the Warburg effect; promoting tumor cell proliferation and invasion; and supporting brain tumorigenesis. Our studies unearthed a novel and important mechanism underlying EGFR-mediated Ras activation in tumor development.
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Haitao
authors.initials: H
authors.lastname: Ji
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Enzyme Engineering and Medical Diagnosis, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China 325035;
authors.forename: Yilin
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Enzyme Engineering and Medical Diagnosis, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China 325035;
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Enzyme Engineering and Medical Diagnosis, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China 325035;
authors.forename: Lianjin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Enzyme Engineering and Medical Diagnosis, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China 325035;
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lyu
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 zhiminlu@mdanderson.org.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D000918:Antibody Specificity / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: C541423:NIBAN2 protein, human; D010750:Phosphoproteins; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins; D010768:Phosphoserine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: EGFR; FAM129B; Ras; Warburg effect; p120-RasGAP