title: SHP-1 protein tyrosine phosphatase associates with the adaptor protein CrkL.
abstract: SHP-1, encoded by the PTPN6 gene, is a protein tyrosine phosphatase with two src-homology-2 (SH2) domains that is implicated as providing suppression of hematopoietic malignancies. A number of reports have shown protein-protein interactions between SHP-1 SH2 domains and tyrosine-phosphorylated proteins. However, despite its having three proline-rich, potential SH3-binding motifs, no reports of protein-protein interactions through src-homology-3 (SH3)-binding domains with SHP-1 have been described. Herein we show that the SH3 domain-containing CT10 regulator of kinase-like (CrkL) adaptor protein associates with SHP-1. We also provide results that suggest this association is due to CrkL binding to PxxP domains located at amino acid residues 158-161 within the SHP-1 C-terminal SH2 domain, and amino acid residues 363-366 within its phosphatase domain. This study is the first to identify and define an interaction between SHP-1 and an SH3 domain-containing protein. Our findings provide an alternative way that SHP-1 can be linked to potential substrates.
authors.affiliation: Cell and Molecular Biology, Toronto General Research Institute, Toronto, Ontario, Canada.
authors.forename: Sevan
authors.initials: S
authors.lastname: Evren
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Ma
authors.forename: Darinka
authors.initials: D
authors.lastname: Sakac
authors.forename: Donald R
authors.initials: DR
authors.lastname: Branch
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D020816:Amino Acid Motifs; D045744:Cell Line, Tumor; D006801:Humans; D008970:Molecular Weight; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D009687:Nuclear Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6