title: Docking interactions of hematopoietic tyrosine phosphatase with MAP kinases ERK2 and p38α.
abstract: Hematopoietic tyrosine phosphatase (HePTP) regulates orthogonal MAP kinase signaling cascades by dephosphorylating both extracellular signal-regulated kinase (ERK) and p38. HePTP recognizes a docking site (D-recruitment site, DRS) on its targets using a conserved N-terminal sequence motif (D-motif). Using solution nuclear magnetic resonance spectroscopy and isothermal titration calorimetry, we compare, for the first time, the docking interactions of HePTP with ERK2 and p38α. Our results demonstrate that ERK2-HePTP interactions primarily involve the D-motif, while a contiguous region called the kinase specificity motif also plays a key role in p38α-HePTP interactions. D-Motif-DRS interactions for the two kinases, while similar overall, do show some specific differences.
authors.affiliation: Department of Chemistry, The City College of New York, New York, NY 10031, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Piserchio
authors.forename: Dana M
authors.initials: DM
authors.lastname: Francis
authors.forename: Dorothy
authors.initials: D
authors.lastname: Koveal
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Dalby
authors.forename: Rebecca
authors.initials: R
authors.lastname: Page
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Peti
authors.forename: Ranajeet
authors.initials: R
authors.lastname: Ghose
mesh_terms: D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry*; D048308:Mitogen-Activated Protein Kinase 14 / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000737:chemistry*
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048308:Mitogen-Activated Protein Kinase 14; C502159:PTPN7 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor