RGD Reference Report - Consensus substrate sequence for protein-tyrosine phosphatase receptor type Z. - Rat Genome Database

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Consensus substrate sequence for protein-tyrosine phosphatase receptor type Z.

Authors: Fujikawa, A  Fukada, M  Makioka, Y  Suzuki, R  Chow, JP  Matsumoto, M  Noda, M 
Citation: Fujikawa A, etal., J Biol Chem. 2011 Oct 28;286(43):37137-46. doi: 10.1074/jbc.M111.270140. Epub 2011 Sep 2.
RGD ID: 9590130
Pubmed: PMID:21890632   (View Abstract at PubMed)
PMCID: PMC3199461   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M111.270140   (Journal Full-text)

Protein-tyrosine phosphatase receptor type Z (Ptprz) has multiple substrate proteins, including G protein-coupled receptor kinase-interactor 1 (Git1), membrane-associated guanylate kinase, WW and PDZ domain-containing 1 (Magi1), and GTPase-activating protein for Rho GTPase (p190RhoGAP). We have identified a dephosphorylation site at Tyr-1105 of p190RhoGAP; however, the structural determinants employed for substrate recognition of Ptprz have not been fully defined. In the present study, we revealed that Ptprz selectively dephosphorylates Git1 at Tyr-554, and Magi1 at Tyr-373 and Tyr-858 by in vitro and cell-based assays. Of note, the dephosphorylation of the Magi1 Tyr-858 site required PDZ domain-mediated interaction between Magi1 and Ptprz in the cellular context. Alignment of the primary sequences surrounding the target phosphotyrosine residue in these three substrates showed considerable similarity, suggesting a consensus motif for recognition by Ptprz. We then estimated the contribution of surrounding individual amino acid side chains to the catalytic efficiency by using fluorescent peptides based on the Git1 Tyr-554 sequence in vitro. The typical substrate motif for the catalytic domain of Ptprz was deduced to be Glu/Asp-Glu/Asp-Glu/Asp-Xaa-Ile/Val-Tyr(P)-Xaa (Xaa is not an acidic residue). Intriguingly, a G854D substitution of the Magi1 Tyr-858 site matching better to the motif sequence turned this site to be susceptible to dephosphorylation by Ptprz independent of the PDZ domain-mediated interaction in cells. Furthermore, we found by database screening that the substrate motif is present in several proteins, including paxillin at Tyr-118, its major phosphorylation site. Expectedly, we verified that Ptprz efficiently dephosphorylates paxillin at this site in cells. Our study thus provides key insights into the molecular basis for the substrate recognition of Ptprz.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
peptidyl-tyrosine dephosphorylation  IDA 9590130 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein tyrosine phosphatase activity  IDA 9590130 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptprz1  (protein tyrosine phosphatase, receptor type Z1)


Additional Information