title: BCCIP associates with the receptor protein tyrosine phosphatase PTPmu.
abstract: The receptor protein tyrosine phosphatase PTPmu belongs to a family of adhesion molecules that contain cell-cell adhesion motifs in their extracellular segments and catalytic domains within their intracellular segments. The ability of PTPmu both to mediate adhesion and exhibit enzymatic activity makes PTPmu an excellent candidate to transduce signals in response to cell-cell adhesion. In an effort to identify downstream signaling partners of PTPmu, we performed a modified yeast two-hybrid screen using the first tyrosine phosphatase domain of PTPmu as bait. We isolated an interacting clone encoding BRCA2 and CDKN1A interacting protein (BCCIP) from a HeLa cell library. BCCIP is a p21 and BRCA2 interacting protein that has been shown to play roles in both cell cycle arrest and DNA repair. In this manuscript, we confirm the interaction between BCCIP and PTPmu identified in yeast using in vitro biochemical studies and characterize BCCIP as a PTPmu binding protein. We demonstrate that BCCIP is phosphorylated by the Src tyrosine kinase and dephosphorylated by the PTPmu tyrosine phosphatase in vitro. Furthermore, we show that BCCIP is required for both the permissive and repulsive functions of PTPmu in neurite outgrowth assays, suggesting BCCIP and PTPmu are in a common signal transduction pathway.
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4960, USA.
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Phillips-Mason
authors.forename: Tracy
authors.initials: T
authors.lastname: Mourton
authors.forename: Denice L
authors.initials: DL
authors.lastname: Major
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016501:Neurites; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C415366:BCCIP protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D019061:src-Family Kinases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
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