Docking interactions of hematopoietic tyrosine phosphatase with MAP kinases ERK2 and p38α

Biochemistry. 2012 Oct 16;51(41):8047-9. doi: 10.1021/bi3012725. Epub 2012 Oct 5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Mitogen-Activated Protein Kinase 1 / chemistry*
  • Mitogen-Activated Protein Kinase 14 / chemistry*
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Tyrosine Phosphatases, Non-Receptor / chemistry*


  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 14
  • PTPN7 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor