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
The Journal of biological chemistry
November 6, 1998
- Agency: NHLBI NIH HHS, Id: R01 HL57393
- Amino Acid Sequence
- Base Sequence
- Blotting, Northern
- Carrier Proteins
- Cell Line
- Chromatography, High Pressure Liquid
- Cloning, Molecular
- DNA, Complementary
- Intracellular Signaling Peptides and Proteins
- Molecular Sequence Data
- 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
- Noonan syndrome 1 is related to genes PTPN11, PTP2C, SHP2, NS1 which are autosomal dominant according to the OMIM database.
- Leukemia, juvenile myelomonocytic is related to genes PTPN11, PTP2C, SHP2, NS1.
- Metachondromatosis is related to genes PTPN11, PTP2C, SHP2, NS1 which are autosomal dominant according to the OMIM database.
- LEOPARD syndrome 1 is related to genes PTPN11, PTP2C, SHP2, NS1 which are autosomal dominant according to the OMIM database.