PKB/Akt-Dependent Regulation of Cell Motility

The prosurvival activity of phosphoinositide 3 kinase (PI3K)/Akt (also known as protein kinase B, PKB) pathway has been investigated in great detail in human physiology and disease. Accumulating evidence is emerging that this signaling axis also actively engages with the migratory process in motile cells, including metastatic cancer cells. Interference with the role of PI3K/Akt-mediated cell motility impairs cellular development and attenuates malignant progression of cancer metastasis. Because metastasis is responsible for 90% of mortality in cancer patients, the acceleration of cancer cell spreading observed in association with hyperactivation of the PI3K pathway, triggered for example by chemotherapy/radiotherapy in the clinic, has heightened awareness of the conflict between "good drugs” and unfavorable effects. Here, we discuss recent studies on PI3K/Akt-regulated cell motility in both physiological and pathological settings, with the aim of a better understanding of how activities of the PI3K/Akt axis initiate and transmit "migratory signals” that stimulate cell movement. We focus in particular on its direct influence on cell migration and invasion, epithelial-mesenchymal transition, and cancer metastasi

PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis

New therapeutic approaches to counter the increasing prevalence of obesity and type 2 diabetes mellitus are in high demand. Deregulation of the phosphoinositide-3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT), mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) pathways, which are essential for glucose homeostasis, often results in obesity and diabetes. Thus, these pathways should be attractive therapeutic targets. However, with the exception of metformin, which is considered to function mainly by activating AMPK, no treatment for the metabolic syndrome based on targeting protein kinases has yet been developed. By contrast, therapies based on the inhibition of the PI3K/AKT and MAPK pathways are already successful in the treatment of diverse cancer types and inflammatory diseases. This contradiction prompted us to review the signal transduction mechanisms of PI3K/AKT, MAPK and AMPK and their roles in glucose homeostasis, and we also discuss current clinical implication

PromoterPlot: a graphical display of promoter similarities by pattern recognition

PromoterPlot (http://promoterplot.fmi.ch) is a web-based tool for simplifying the display and processing of transcription factor searches using either the commercial or free TransFac distributions. The input sequence is a TransFac search (public version) or FASTA/Affymetrix IDs (local install). It uses an intuitive pattern recognition algorithm for finding similarities between groups of promoters by dividing transcription factor predictions into conserved triplet models. To minimize the number of false-positive models, it can optionally exclude factors that are known to be unexpressed or inactive in the cells being studied based on microarray or proteomic expression data. The program will also estimate the likelihood of finding a pattern by chance based on the frequency observed in a control set of mammalian promoters we obtained from Genomatix. The results are stored as an interactive SVG web page on our serve

PromoterPlot: a graphical display of promoter similarities by pattern recognition

PromoterPlot () is a web-based tool for simplifying the display and processing of transcription factor searches using either the commercial or free TransFac distributions. The input sequence is a TransFac search (public version) or FASTA/Affymetrix IDs (local install). It uses an intuitive pattern recognition algorithm for finding similarities between groups of promoters by dividing transcription factor predictions into conserved triplet models. To minimize the number of false-positive models, it can optionally exclude factors that are known to be unexpressed or inactive in the cells being studied based on microarray or proteomic expression data. The program will also estimate the likelihood of finding a pattern by chance based on the frequency observed in a control set of mammalian promoters we obtained from Genomatix. The results are stored as an interactive SVG web page on our server

Integrated Akt/PKB Signaling in Immunomodulation and Its Potential Role in Cancer Immunotherapy

T cell development and maturation involve a variety of defined and coordinated developmental stages under the control of a variety of signaling networks. They function as the major mediator in cell-based immunity that defends against pathogen infections and executes immune surveillance against tumor cells. Protein kinase B (PKB, also called Akt) is central to multiple signaling pathways and transduces extracellular signals to dictate cellular responses towards proliferation, migration, anti-apoptosis, and maintenance of metabolic homeostasis. Although the prosurvival function of PKB was thought to be responsible for most of the functions regulated by PKB, emerging evidence has started to dissect its role in immunomodulation. More importantly, hyperactivation of PKB in cancer stroma frequently occurs in patients treated clinically with targeted cancer therapies, where it acts as a key mediator involved in the trapping of host immune cells in the vicinity of tumors, which supports cancer cell invasion and the escape of cancer cells from host immune surveillance. Encouragingly, recent studies have shown that inhibition of PKB improves the recognition of cancer cells by the host immune system, indicating a potential clinical strategy to rekindle the suppressed host immune response through the specific targeting of PKB. In this review, we explore how PKB signaling contributes to T cell development and cellular immune responses and discuss the mechanistic roles that PKB plays in the creation of immunosuppressive conditions and the escaping of immune recognition in the microenvironment of cance

Athletes’ Expectations About Sport-Injury Rehabilitation: A Cross-Cultural Study

Context: Athletes enter injury rehabilitation with certain expectations about the recovery process, outcomes, and the professional providing treatment. Their expectations influence the effectiveness of the assistance received and affect the overall rehabilitation process. Expectations may vary depending on numerous factors such as sport experience, gender, sport-type and cultural background. Unfortunately, limited information is available on athletes’ expectations about sport injury rehabilitation. Objective: To examine possible differences in athletes’ expectations about sport injury rehabilitation based on their country of residence and type of sport (physical contact versus non-physical contact). Design: A cross-sectional design. Setting: Recreational, collegiate, and professional athletes from the United States (US), United Kingdom (UK) and Finland were surveyed. Participants: Of the 1209 athletes ranging from 12 to 80 years of age (Mage = 23.46 ± 7.91), of which 529 US [80%], 253 UK [86%], and 199 Finnish [82%] provided details of their geographical location, were included in the final analyses. Main Outcome Measures: The Expectations about Athletic Training (EAAT) questionnaire was used to determine athletes’ expectations about personal commitment, facilitative conditions, and the expertise of the sports medicine professional (Clement et al., 2012). Results: 3x2 MANCOVA revealed significant main effects for country (p = .0001, ηp2 = .055) and sport type (p = .0001, ηp2 = .023). Specifically, US athletes were found to have higher expectations of personal commitment and facilitative conditions than their UK and Finnish counterparts. Athletes participating in physical contact sports had higher expectations of facilitative conditions and the expertise of the sports medicine professional (SMP) as compared to athletes participating in non-physical contact sports. Conclusions: SMPs, especially those in the US, should consider the sport and environment when providing services. In addition, SMPs need to highlight and demonstrate their expertise durin