The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2.

CD2, a cell surface glycoprotein expressed on T cells and natural killer cells, can couple to signaling pathways that result in T cell proliferation. An Src-like protein tyrosine kinase, p56lck, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity of p56lck, suggesting that an interaction with p56lck contributes to CD2-mediated signaling. Herein, we investigate the mechanism by which CD2 associates with p56lck. We demonstrate that CD2 and p56lck associate when coexpressed in nonlymphoid cells, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p56lck mediates its interactions with CD2. Using truncation mutants of CD2, we identify two regions in the cytoplasmic domain of CD2 involved in binding p56lck. Each region contains a proline-rich sequence that, in the form of a synthetic peptide, directly binds p56lck. Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p56lck

Elevated c-Src is linked to altered cell–matrix adhesion rather than proliferation in KM12C human colorectal cancer cells

Elevated expression and/or activity of c-Src, the prototype of the Src family of protein tyrosine kinases, is associated with the development of human colon cancer. However, despite the known pleiotropic effects of these kinases in promoting (a) cell growth downstream of growth factor receptors, and (b) the dynamic regulation of integrin adhesions in fibroblast model systems, their precise role in epithelial cancer cells is unknown. Here we addressed whether elevated expression and activity of cellular Src alters cell proliferation and/or cell–matrix adhesion in cancer cells from the Fidler model of colorectal metastasis. Although elevated Src correlates with ability to metastasise to the liver after intrasplenic injection, we found that this was not linked to enhanced growth, either in vitro or in vivo as sub-cutaneous tumours. However, elevated Src was associated with enhanced attachment to extracellular matrix. In addition, adhesion to fibronectin, was suppressed by agents that inhibited Src activity, while enforced elevation of Src in non-metastatic cells was sufficient to stimulate adhesion to fibronectin and enhanced assembly of adhesion complexes, without influencing cell growth. Thus, we conclude that one role of elevated Src in human colon cancer cells is to modulate integrin-dependent cell–matrix attachment and formation of adhesion structures, which may, in turn, influence cell motility and integrin-dependent cellular responses

Self-reported safety belt use among emergency department patients in Boston, Massachusetts

BACKGROUND: Safety belt use is 80% nationally, yet only 63% in Massachusetts. Safety belt use among potentially at-risk groups in Boston is unknown. We sought to assess the prevalence and correlates of belt non-use among emergency department (ED) patients in Boston. METHODS: A cross-sectional survey with systematic sampling was conducted on non-urgent ED patients age ≥18. A closed-ended survey was administered by interview. Safety belt use was defined via two methods: a single-item and a multiple-item measure of safety belt use. Each was scored using a 5-point frequency scale. Responses were used to categorize safety belt use as 'always' or less than 'always'. Outcome for multivariate logistic regression analysis was safety belt use less than 'always'. RESULTS: Of 478 patients approached, 381 (80%) participated. Participants were 48% female, 48% African-American, 40% White, median age 39. Among participants, 250 (66%) had been in a car crash; 234 (61%) had a valid driver's license, and 42 (11%) had been ticketed for belt non-use. Using two different survey measures, a single-item and a multiple-item measure, safety belt use 'always' was 51% and 36% respectively. According to separate regression models, factors associated with belt non-use included male gender, alcohol consumption >5 drinks in one episode, riding with others that drink and drive, ever receiving a citation for belt non-use, believing that safety belt use is 'uncomfortable', and that 'I just forget', while 'It's my usual habit' was protective. CONCLUSION: ED patients at an urban hospital in Boston have considerably lower self-reported safety belt use than state or national estimates. An ED-based intervention to increase safety belt use among this hard-to-reach population warrants consideration

Egg rejection in blackbirds Turdus merula: a by-product of conspecific parasitism or successful resistance against interspecific brood parasites?

Traditional theory assumes that egg recognition and rejection abilities arise as a response against interspecific brood parasitism (IBP). However, rejection also appears in some species that are currently not exploited by interspecific parasites, such as Turdus thrushes. Recent evidences suggest that rejection abilities evolved in these species as a response to conspecific brood parasitism (CBP). To test these two alternative hypotheses, we performed an experimental study by parasitizing nests of the common blackbird (Turdus merula) with conspecifics or heterospecific eggs under different risk of parasitism (presence of interspecific or conspecific parasites near the nest). Common blackbird is a potential host of the common cuckoo (Cuculus canorus) but suffers low levels of CBP too. Results: We found that blackbirds were able to recognize and eject heterospecific eggs at high rates whereas most of conspecifics eggs were not recognized and, therefore, accepted. Ejection rates of conspecific eggs did not exceed 13 %, even in situations of high risk of CBP (blackbird female placed near the nest), which contradict the main prediction derived from the CBP hypothesis. Conversely, ejection rates of experimental eggs simulating IBP were much higher (80–100 %). Furthermore, female blackbirds were more aggressive towards cuckoos than towards blackbird dummies. Conclusions: Our results considered together support the IBP hypothesis, indicating that recognition and rejection of parasitic eggs in blackbirds have probably evolved due to previous cuckoo parasitism. The current absence of IBP in blackbirds may be due to the highly efficient rejection abilities in this species. Thus, these abilities have been retained in absence of brood parasitism as a consequence of the low costs involved for blackbirds, resulting in a successful resistance against interspecific brood parasitism.Financial support has been provided by the Consejería Economía, Innovación, Ciencia y Empleo. Junta de Andalucia (research project CVI-6653)