Src family tyrosine kinases (SFKs) are critical players in normal and aberrant biological processes. While phosphorylation importantly-regulates SFKs at two known tyrosines, large-scale phosphoproteomics have revealed four additional tyrosines commonly-phosphorylated in SFKs. We found these novel tyrosines to be autophosphorylation sites. Mimicking phosphorylation at the site C-terminal to the activation loop decreased Fyn activity. Phosphomimetics and direct phosphorylation at the three SH2 domain sites increased Fyn activity while reducing phosphotyrosine-dependent interactions. While 68% of human SH2 domains exhibit conservation of at least one of these tyrosines, few have been found phosphorylated except when found in cis to a kinase domain.

Fyn is a Src Family Kinase (SFK) important for cerebral cortical development. Its SH2 domain tightly regulates catalytic activity via interaction with an inhibitory phosphotyrosine (Y531) in the C‐terminus. Recent mass spectrometry studies identified novel phosphotyrosines (pY185, pY213, pY214) in Fyn's SH2 domain which may regulate Fyn's activity. The goal of this project is to analyze whether newly identified phosphotyrosines in Fyn's SH2 domain alter neuronal migration in vivo. Transgenic worms expressing wild type human Fyn or a Fyn SH2 binding mutant (R176E) in mechanosensory neurons were engineered to determine if Fyn expression rescues the neuronal migration phenotype in an SFK (src‐1) null mutant. A transgenic construct was also engineered containing phosphomimetic mutations at Y185, Y213, and Y214. Fyn expression in transgenic lines was validated by Western blot, and preliminary analysis of neuronal migration in L4 stage C. elegans showed no alterations from non‐transgenic worms. Transgenic lines will be crossed with src‐1 mutants and analyzed for rescue or altered rescue of the src‐1 migration phenotype to determine whether phosphotyrosines within Fyn's SH2 domain are important in the regulation of neuronal development. This project was supported by the Vermont Genetics Network through grant #8P20GM103449 from the INBRE Program of the NIGMS and NCRR, components of the NIH.

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Athletes commonly sustain high-energy direct impact injuries to the shoulder, with acromioclavicular joint (ACJ) injuries accounting for over half. Ipsilateral ACJ injury and diaphyseal clavicle fracture occur nearly 7% of the time. There is limited literature offering treatment suggestions for this unique injury pattern and limited evidence providing guidance to suggest which injury patterns should be treated operatively or nonoperatively. Here, we present successful treatment of a high-level athlete utilizing a Knotless TightRope XP placed through a superior clavicle plate with successful return to full activity at 6 months postoperation. The TightRope technique offers the ability to augment through a preexisting superior clavicular plate in a low-profile manner and promote easy suture tensioning to obtain and maintain reduction of the injured ACJ.