title: Phosphatidylinositol phosphate kinase type Igamma directly associates with and regulates Shp-1 tyrosine phosphatase.
abstract: Tyrosine phosphorylation plays a critical role in many regulatory aspects of cellular signaling, and dephosphorylation of phosphotyrosine residues is crucial for termination of signals initiated by tyrosine kinases. Previous work has shown that the tyrosine kinase Src phosphorylates Tyr644 on phosphatidylinositol phosphate kinase type I (PIPKI) gamma661 in a focal adhesion kinase-dependent manner. Phosphorylation of this residue is essential for high affinity binding of PIPKI gamma661 to the focal adhesion protein talin and for targeting of PIPKI gamma661 to focal adhesions. A yeast two-hybrid screen performed with the C-terminal 178-amino acid tail of PIPKI gamma661 identified an interaction with the phosphatase domain of the tyrosine phosphatase Shp-1. The interaction between PIPKI gamma661 and Shp-1 was confirmed via co-immunoprecipitation from HEK293 cell lysates. In addition, Src-phosphorylated PIPKI gamma661 is a substrate for Shp-1, and Shp-1 modulates both the association between PIPKI gamma661 and talin and the targeting of PIPKI gamma661 to focal adhesions in mammalian cells. Finally, we showed that Shp-1 phosphatase activity is inhibited by the product of PIPKI gamma661, phosphatidylinositol 4,5-bisphosphate, in vitro. These combined results suggest a model in which the reciprocal actions of Src tyrosine kinase and Shp-1 tyrosine phosphatase dynamically regulate the association between PIPKI gamma661 and talin.
authors.affiliation: Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
authors.forename: Shawn F
authors.initials: SF
authors.lastname: Bairstow
authors.forename: Kun
authors.initials: K
authors.lastname: Ling
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D015778:Minor Histocompatibility Antigens; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D014443:Tyrosine; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse