Integrin β3 Crosstalk with VEGFR Accommodating Tyrosine Phosphorylation as a Regulatory Switch

Integrins mediate cell adhesion, migration, and survival by connecting intracellular machinery with the surrounding extracellular matrix. Previous studies demonstrated the importance of the interaction between β3 integrin and VEGF type 2 receptor (VEGFR2) in VEGF-induced angiogenesis. Here we present in vitro evidence of the direct association between the cytoplasmic tails (CTs) of β3 and VEGFR2. Specifically, the membrane-proximal motif around 801YLSI in VEGFR2 mediates its binding to non-phosphorylated β3CT, accommodating an α-helical turn in integrin bound conformation. We also show that Y747 phosphorylation of β3 enhances the above interaction. To demonstrate the importance of β3 phosphorylation in endothelial cell functions, we synthesized β3CT-mimicking Y747 phosphorylated and unphosphorylated membrane permeable peptides. We show that a peptide containing phospho-Y747 but not F747 significantly inhibits VEGF-induced signaling and angiogenesis. Moreover, phospho-Y747 peptide exhibits inhibitory effect only in WT but not in β3 integrin knock-out or β3 integrin knock-in cells expressing β3 with two tyrosines substituted for phenylalanines, demonstrating its specificity. Importantly, these peptides have no effect on fibroblast growth factor receptor signaling. Collectively these data provide novel mechanistic insights into phosphorylation dependent cross-talk between integrin and VEGFR2

Measurement of the CKM angle γ\gamma using B0→DK∗0B^0 \rightarrow D K^{*0} with D→KS0π+π−D \rightarrow K^0_S \pi^+ \pi^- decays

A model-dependent amplitude analysis of the decay $B^0\rightarrow D(K^0_S\pi^+\pi^-) K^{*0}$ is performed using proton-proton collision data corresponding to an integrated luminosity of 3.0fb$^{-1}$, recorded at $\sqrt{s}=7$ and $8 TeV$ by the LHCb experiment. The CP violation observables $x_{\pm}$ and $y_{\pm}$, sensitive to the CKM angle $\gamma$, are measured to be \begin{eqnarray*} x_- &=& -0.15 \pm 0.14 \pm 0.03 \pm 0.01, y_- &=& 0.25 \pm 0.15 \pm 0.06 \pm 0.01, x_+ &=& 0.05 \pm 0.24 \pm 0.04 \pm 0.01, y_+ &=& -0.65^{+0.24}_{-0.23} \pm 0.08 \pm 0.01, \end{eqnarray*} where the first uncertainties are statistical, the second systematic and the third arise from the uncertainty on the $D\rightarrow K^0_S \pi^+\pi^-$ amplitude model. These are the most precise measurements of these observables. They correspond to $\gamma=(80^{+21}_{-22})^{\circ}$ and $r_{B^0}=0.39\pm0.13$, where $r_{B^0}$ is the magnitude of the ratio of the suppressed and favoured $B^0\rightarrow D K^+ \pi^-$ decay amplitudes, in a $K\pi$ mass region of $\pm50 MeV$ around the $K^*(892)^0$ mass and for an absolute value of the cosine of the $K^{*0}$ decay angle larger than $0.4$.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-007.htm

Search for dark photons produced in 13 TeV pppp collisions

Searches are performed for both promptlike and long-lived dark photons, A 0 , produced in proton-proton collisions at a center-of-mass energy of 13 TeV, using A 0 → μ þ μ − decays and a data sample corresponding to an integrated luminosity of 1 . 6 fb − 1 collected with the LHCb detector. The promptlike A 0 search covers the mass range from near the dimuon threshold up to 70 GeV, while the long-lived A 0 search is restricted to the low-mass region 214 <m ð A 0 Þ < 350 MeV. No evidence for a signal is found, and 90% confidence level exclusion limits are placed on the γ – A 0 kinetic-mixing strength. The constraints placed on promptlike dark photons are the most stringent to date for the mass range 10 . 6 <m ð A 0 Þ < 70 GeV, and are comparable to the best existing limits for m ð A 0 Þ < 0 . 5 GeV. The search for long-lived dark photons is the first to achieve sensitivity using a displaced-vertex signature