MAP4K Family Kinases in Immunity and Inflammation

Advances in Immunology
Huai-Chia ChuangTse-Hua Tan

Abstract

MAP kinase kinase kinase kinases (MAP4Ks) belong to the mammalian Ste20-like family of serine/threonine kinases. MAP4Ks including MAP4K1/HPK1, MAP4K2/GCK, MAP4K3/GLK, MAP4K4/HGK, MAP4K5/KHS, and MAP4K6/MINK have been reported to induce JNK activation through activating the MAP3K-MAP2K cascade. The physiological roles of MAP4Ks in immunity and inflammation are largely unknown until recent studies using biochemical approaches and knockout mice. Surprisingly, JNK is not the major target of MAP4Ks in immune cells; MAP4Ks regulate immune responses through novel targets. HPK1 inhibits T-cell receptor (TCR) signaling and B-cell receptor signaling via inducing phosphorylation/ubiquitination of SLP-76 and BLNK, respectively. GLK activates TCR signaling through phosphorylating/activating PKCθ. T-cell-mediated immune responses and Th17-mediated experimental autoimmune diseases are enhanced in HPK1 knockout mice but ameliorated in GLK knockout mice. Consistently, HPK1 levels are decreased in peripheral blood mononuclear cells and T cells from patients with psoriatic arthritis and systemic lupus erythematosus (SLE), respectively. Moreover, GLK levels are increased in T cells from patients with SLE, rheumatoid arthritis, or adult-onset Still...Continue Reading

Citations

Jan 8, 2017·Journal of Biomedical Science·Huai-Chia Chuang, Tse-Hua Tan
Jul 13, 2018·Chembiochem : a European Journal of Chemical Biology·Mubarak A AlAmriYoucef Mehellou
Nov 27, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wenwen ChenQing Chang
Jul 19, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Huai-Chia ChuangTse-Hua Tan
Sep 17, 2019·Technology in Cancer Research & Treatment·Zhenjie BaiJicheng Zhou
Feb 27, 2016·Oncotarget·Huai-Chia ChuangTse-Hua Tan
Jul 15, 2018·Scientific Reports·Anello Marcello PomaGabriella Fontanini
Aug 17, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chia-Yu YangTse-Hua Tan
Sep 9, 2020·ELife·Sansana Sawasdikosol, Steven Burakoff
Nov 2, 2016·Cell & Bioscience·Xuan GaoJing Hu
Oct 24, 2019·Journal of Biomedical Science·Huai-Chia Chuang, Tse-Hua Tan
Aug 28, 2020·Frontiers in Plant Science·Lixia Pan, Ive De Smet
Oct 15, 2019·PeerJ·Siliang ChenYuehong Zheng
Feb 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wenliang WangGolnaz Vahedi
Aug 23, 2019·Cancer Research·Huai-Chia ChuangTse-Hua Tan
Jan 8, 2021·Journal for Immunotherapy of Cancer·Dan YouJinqi Liu
Feb 21, 2021·Bioorganic & Medicinal Chemistry Letters·Jiamin ZhengGe Zou
Nov 12, 2020·Journal of Structural Biology·Lorenzo SoiniChristian Ottmann
Mar 19, 2021·ACS Medicinal Chemistry Letters·Andrew P DegnanMark D Wittman
May 2, 2021·Seminars in Arthritis and Rheumatism·Xiangrong WuWenhua Liang
May 7, 2021·Expert Opinion on Therapeutic Patents·Ian D Linney, Neelu Kaila
Sep 9, 2021·Medical Oncology·Mohadeseh ShayeghanMohammad Amin Javidi
Sep 7, 2021·Frontiers in Plant Science·Lixia PanIve De Smet

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