Fgr but not Syk tyrosine kinase is a target for beta2 integrin-induced c-Cbl-mediated ubiquitination in adherent human neutrophils

An early and critical event in beta2 integrin signalling during neutrophil adhesion is activation of Src tyrosine kinases and Syk. In the present study, we report Src kinase-dependent beta2 integrin-induced tyrosine phosphorylation of Cbl occurring in parallel with increased Cbl-associated tyrosine kinase activity. These events concurred with activation of Fgr and, surprisingly, also with dissociation of this Src tyrosine kinase from Cbl. Moreover, the presence of the Src kinase inhibitor PP1 in an in vitro assay had only a limited effect on the Cbl-associated kinase activity. These results suggest that an additional active Src-dependent tyrosine kinase associates with Cbl. The following observations imply that Syk is such a kinase: (i) beta2 integrins activated Syk in a Src-dependent manner, (ii) Syk was associated with Cbl much longer than Fgr was, and (iii) the Syk inhibitor piceatannol (3,4,3´,5´-tetrahydroxy-trans-stilbene) abolished the Cbl-associated kinase activity in an in vitro assay. Effects of the mentioned interactions between these two kinases and Cbl may be related to the finding that Cbl is a ubiquitin E3 ligase. Indeed, we detected beta2 integrin-induced ubiquitination of Fgr that, similar to the phosphorylation of Cbl, was abolished in cells pretreated with PP1. However, the ubiquitination of Fgr did not cause any apparent degradation of the protein. In contrast with Fgr, Syk was not modified by the E3 ligase. Thus Cbl appears to be essential in beta2 integrin signalling, first by serving as a matrix for a subsequent agonist-induced signalling interaction between Fgr and Syk, and then by mediating ubiquitination of Fgr which possibly affects its interaction with Cbl.

The influence of experience on the research competencies of university professors

Implementation of EHEA, among others, motivates a transforming process in universities and promotes changes in the professor’s tasks. This events, promote changes to which the university professor has to adapt, meaning this to acquire and to develop new competencies to respond correctly to new professional tasks that are demanded. To design training plans in accordance to the new training needs, and to establish referents in accreditation, selection and promotion protocols appear to be necessary to define the new competences profile professors have to face in order to develop their teaching, research and management tasks suitably, and according to their professional settings and professional development stage. A qualitative research was developed to define the emerging competence profile. Quantitative and qualitative methods were mixed as well as different tools (questionnaires, interviews and focus groups) and sources (faculty, experts and students). This article only shows the results obtained from professors (expert and novice) in the 4 research competencies analyzed (design, development and assessment of projects; organization and management of scientific events; development of scientific material; communication and dissemination of scientific knowledges) and the most significant dates of the 30 competency units that compose them. Results show significant differences of self-perception of current competency domain level between novice faculty and expert faculty. These results help us to establish the priority training areas to the faculty according to their professional development stage.