title: Interaction of kinase-interaction-motif protein tyrosine phosphatases with the mitogen-activated protein kinase ERK2.
abstract: The mitogen-activation protein kinase ERK2 is tightly regulated by multiple phosphatases, including those of the kinase interaction motif (KIM) PTP family (STEP, PTPSL and HePTP). Here, we use small angle X-ray scattering (SAXS) and isothermal titration calorimetry (ITC) to show that the ERK2:STEP complex is compact and that residues outside the canonical KIM motif of STEP contribute to ERK2 binding. Furthermore, we analyzed the interaction of PTPSL with ERK2 showing that residues outside of the canonical KIM motif also contribute to ERK2 binding. The integration of this work with previous studies provides a quantitative and structural map of how the members of a single family of regulators, the KIM-PTPs, differentially interact with their corresponding MAPKs, ERK2 and p38α.
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Francis
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Koveal
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Antoni
authors.initials: A
authors.lastname: Tortajada
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Page
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, United States of America; Department of Chemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Peti
mesh_terms: D054637:Dual-Specificity Phosphatases / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism*; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism; D011485:Protein Binding; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism*; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7 / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048308:Mitogen-Activated Protein Kinase 14; D054639:Mitogen-Activated Protein Kinase Phosphatases; C439065:DUSP16 protein, human; D054637:Dual-Specificity Phosphatases; C489930:PTPN5 protein, human; C502159:PTPN7 protein, human; C513469:PTPRR protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7