No abstract

Previously, we have demonstrated that the cytoplasmic tyrosine kinase p72syk is coupled to the platelet Fc receptor for IgG (Fc gamma RIIA) (Chacko, G. W., Duchemin, A. M., Coggeshall, K. M., Osborne, J. M., Brandt, J. T., and Anderson, C. L. (1994) J. Biol. Chem. 269, 32435-32440). Further analysis of the platelet activation by Fc gamma RIIA demonstrated that Fc gamma RIIA is also inducibly coupled to the serine/threonine and lipid kinase, phosphoinositide 3-kinase (PI 3-K). activation of platelets with anti-Fc gamma RIIA antibodies resulted in the noncovalent association of PI 3-K with Fc gamma RIIA as well as an increase in Fc gamma RIIA-associated PI 3-K activity. Binding of both p72syk and PI 3-K to Fc gamma RIIA was reconstituted with synthetic phosphopeptides corresponding to the sequence of the atypical immunoreceptor tyrosine-based activation motif (ITAM) in the cytoplasmic domain of Fc gamma RIIA. Our findings demonstrate that coupling of both p72syk and PI. 3-K activities to Fc gamma RIIA is regulated by tyrosine phosphorylation of the ITAM, and we speculate that p72syk might act as an adapter to recruit PI 3-K to activated Fc gamma RIIA.

The ability of a T cell to be activated is critically regulated by the number of TCRs expressed on the plasma membrane. Cell surface TCR expression is influenced by dynamic processes such as synthesis and transport of newly assembled receptors, endocytosis of surface TCR, and recycling to the plasma membrane of internalized receptors. In this study, the internalization of fluorescently labeled anti-TCR Abs was used to analyze constitutive endocytosis of TCRs on T cells, and to investigate the role of the ζ-chain in this process. We found that cell surface TCRs lacking ζ were endocytosed more rapidly than completely assembled receptors, and that reexpression of full-length ζ led to a dose-dependent decrease in the rate of TCR internalization. Rapid TCR internalization was also observed with CD4+CD8+ thymocytes from ζ-deficient mice, whereas TCR internalization on thymocytes from CD3-δ deficient animals was slow, similar to that of wild-type thymocytes. This identifies a specific role for ζ in the regulation of constitutive receptor internalization. Furthermore, chimeric ζ molecules containing non-native intracellular amino acid sequences also led to high levels of TCR expression and reduced TCR cycling. These effects were dependent solely on the length of the intracellular tail, ruling out a role for intracellular ζ-specific interactions with other molecules as a mechanism for regulating TCR internalization. Rather, these findings strongly support a model in which the ζ-chain stabilizes TCR residency on the cell surface, and functions to maintain cell surface receptor expression by sterically blocking internalization sequences in other TCR components.

No abstract

Recently, Wu, Wang, and Evans (2019) proposed a new family of indicators, which measure whether a scientific publication is disruptive to a field or tradition of research. Such disruptive influences are characterized by citations to a focal paper, but not its cited references. In this study, we are interested in the question of convergent validity. We used external criteria of newness to examine convergent validity: In the post-publication peer review system of F1000Prime, experts assess papers whether the reported research fulfills these criteria (e.g., reports new findings). This study is based on 120,179 papers from F1000Prime published between 2000 and 2016. In the first part of the study we discuss the indicators. Based on the insights from the discussion, we propose alternate variants of disruption indicators. In the second part, we investigate the convergent validity of the indicators and the (possibly) improved variants. Although the results of a factor analysis show that the different variants measure similar dimensions, the results of regression analyses reveal that one variant ( DI5) performs slightly better than the others.