BCCIP Associates With the Receptor Protein Tyrosine Phosphatase PTPμ

The receptor protein tyrosine phosphatase PTP mu 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 PTP mu both to mediate adhesion and exhibit enzymatic activity makes PTP mu an excellent candidate to transduce signals in response to cell-cell adhesion. In an effort to identify downstream signaling partners of PTP mu we performed a modified yeast two-hybrid screen using the first tyrosine phosphatase domain of PTP mu 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 PTP mu identified in yeast using in vitro biochemical studies and characterize BCCIP as a PTP mu binding protein. We demonstrate that BCCIP is phosphorylated by the Src tyrosine kinase and dephosphorylated by the PTP mu tyrosine phosphatase in vitro. Furthermore, we show that BCCIP is required for both the permissive and repulsive functions of PTP mu in neurite outgrowth assays, suggesting BCCIP and PTP mu are in a common signal transduction pathway. J. Cell. Biochem. 105: 1059-1072, 2008. (C) 2008 Wiley-Liss, Inc.