Biliary glycoprotein (Bgp, C-CAM, or CD66a) is an immunoglobulin-like cell adhesion molecule and functions as a tumor suppressor protein. We have previously shown that the Bgp1 isoform responsible for inhibition of colonic, liver, prostate, and breast tumor cell growth contains within its cytoplasmic domain two tyrosine residues positioned in immunoreceptor tyrosine-based inhibition motif (ITIM) consensus sequences. Moreover, we determined that these residues, upon phosphorylation, associate with the protein-tyrosine phosphatase SHP-1. In this report, we have further evaluated the structural bases of the association of Bgp1 with Tyr phosphatases. First, we demonstrate that Bgp1 also associates with the SHP-2 Tyr phosphatase, but not with an unrelated Tyr phosphatase, PTP-PEST. Association of Bgp1 and SHP-2 involves the Tyr residues within the Bgp1 ITIM sequences, Val at position ؉3 relative to the second Tyr (Tyr-515), and the SHP-2 N-terminal SH2 domain. In addition, our results indicate that residues ؉4, ؉5, and ؉6 relative to Tyr-515 in the Bgp1 cytoplasmic domain play a significant role in these interactions, as their deletion reduced Bgp1 Tyr phosphorylation and association with SHP-1 and SHP-2 by as much as 80%. Together, these results indicate that both SHP-1 and SHP-2 interact with the Bgp1 cytoplasmic domain via ITIM-like sequences. Furthermore, they reveal that the C-terminal amino acids of Bgp1 are critical for these interactions.

IntroductionChronic lateral epicondylosis (CLE) of the elbow is a prevalent condition among middle-aged people with no consensus on optimal care management but for which surgery is generally accepted as a second intention treatment. Among conservative treatment options, ultrasound (US)-guided fenestration has shown encouraging results that should be explored before surgery is considered. The primary objective of this study is to compare the efficacy of US-guided fenestration with open-release surgery in patients with failure to improve following a minimum 6 months of conservative treatment.Methods and analysisThis study protocol entails a two-arm, single-blinded, randomised, controlled design. Sixty-four eligible patients with clinically confirmed CLE will be assigned to either US-guided fenestration or open-release surgery. Fisher’s exact test will be used to compare the proportion of patients reporting a change of 11/100 points or more in the Patient Rated Tennis Elbow Evaluation score at 6 months, according to an intention-to-treat analysis. Secondary analyses will compare the two treatment groups in terms of pain and disability, functional limitations at work, pain-free grip strength, medication burden, patients’ global impression of change and level of satisfaction at 6 weeks, 3, 6 and 12 months, using mixed linear models for repeated measures or Fisher’s exact test, as appropriate. Finally, recursive partitioning analyses will investigate US and elastography parameters as predictors of treatment success at 6 and 12 months. This data will contribute to evidence-based treatment guidelines for CLE and explore the value of imaging biomarkers to improve risk stratification plans and assist clinicians.Ethics and disseminationThe study has been approved by the Research Ethics Board of our institution on 23 March 2016 (REB 15.327). In case of important protocol modifications, a new version of the protocol with appropriate amendments will be submitted to the REB for approval. Study results will be published in peer-reviewed journals and presented at local, national and international conferences.Trial registration numberNCT02710682.

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