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Purification and cloning of PZR, a binding protein and putative physiological substrate of tyrosine phosphatase SHP-2.

Overexpression of a catalytically inactive mutant of tyrosine phosphatase SHP-2 in 293 cells resulted in hyperphosphorylation of a glycoprotein specifically associated with the enzyme. The protein has been purified to near homogeneity. Based on the amino acid sequences of peptides obtained from the protein, a full-length cDNA was isolated. The cDNA encodes a protein with a single transmembrane segment and a signal sequence. The extracellular portion of the protein contains a single immunoglobulin-like domain displaying 46% sequence identity to that of myelin P0, a major structural protein of peripheral myelin. The intracellular segment of the protein shows no significant sequence identity to any known protein except for two immunoreceptor tyrosine-based inhibitory motifs. We name the protein PZR for protein zero related. Transfection of the PZR cDNA in Jurkat cells gave rise to a protein of expected molecular size. Stimulation of cells with pervanadate resulted in tyrosine phosphorylation of PZR and a near-stoichiometric association of PZR with SHP-2. Northern blotting analyses revealed that PZR is widely expressed in human tissues and is particularly abundant in heart, placenta, kidney, and pancreas. As a binding protein and a putative substrate of SHP-2, PZR protein may have an important role in cell signaling.

Pubmed ID: 9792637

Authors

  • Zhao ZJ
  • Zhao R

Journal

The Journal of biological chemistry

Publication Data

November 6, 1998

Associated Grants

  • Agency: NHLBI NIH HHS, Id: R01 HL57393

Mesh Terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • DNA, Complementary
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Phosphoproteins
  • Precipitin Tests
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Sequence Homology, Amino Acid
  • Substrate Specificity