Detection of partially phosphorylated forms of ERK by monoclonal antibodies reveals spatial regulation of ERK activity by phosphatases

FEBS Letters

Yung, Yuval²  Dolginov, Yakov¹  Yao, Zhong²  Lando, Zeev¹  Ridner, Gabriela²  Seger, Rony²  Hanoch, Tamar²  Zharhary, Dorit¹ 

[1] Sigma Israel Chemicals Ltd., Rehovot, Israel;Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel

关键词: Signal transduction;    Phosphatase;    Kinase;    Anti-phospho-antibody;    Mitogen-activated protein kinase;    MAPK;    mitogen-activated protein kinase;    ERK;    extracellular signal-regulated kinase;    PBS;    phosphate-buffered saline;    EGF;    epidermal growth factor;    FCS;    fetal calf serum;    BSA;    bovine serum albumin;    TEY peptide;    11-mer peptide derived from the activation loop of ERK;    PT-;    PY-;    NP- and DP-TEY;    Thr-;    Tyr-;    non- and doubly phosphorylated TEY peptide;    respectively;    Tyr;    tyrosine;    Ser;    serine;    Thr;    threonine;    mAb;    monoclonal antibody;    pAb;    polyclonal antibody;   

DOI  :  10.1016/S0014-5793(00)01191-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

When cells are stimulated by mitogens, extracellular signal-regulated kinase (ERK) is activated by phosphorylation of its regulatory threonine (Thr) and tyrosine (Tyr) residues. The inactivation of ERK may occur by phosphatase-mediated removal of the phosphates from these Tyr, Thr or both residues together. In this study, antibodies that selectively recognize all combinations of phosphorylation of the regulatory Thr and Tyr residues of ERK were developed, and used to study the inactivation of ERK upon mitogenic stimulation. We found that inactivation of ERK in the early stages of mitogenic stimulation involves separate Thr and Tyr phosphatases which operate differently in the nucleus and in the cytoplasm. Thus, ERK is differentially regulated in various subcellular compartments to secure proper length and strength of activation, which eventually determine the physiological outcome of many external signals.

【 授权许可】

Unknown