Intracellular signaling by receptor tyrosine kinases regulates many different aspects of cell behavior. Recent studies in our laboratory and others have demonstrated that the EphA2 receptor tyrosine kinase critically regulates tumor cell growth, migration and invasiveness. Although the cellular consequences of EphA2 signaling have been the focus of recent attention, the biochemical changes that are triggered by ligand-mediated activation of EphA2 remain largely unknown. Herein, we demonstrate that ligand stimulation of EphA2 promotes the nucleus translocation and phosphorylation of ERK kinases, followed by an increase in nuclear induction of the Elk-1 transcription factor. Ligand-mediated activation allows EphA2 to form a molecular complex with the SHC and GRB2 adaptor proteins. Specifically, we demonstrate that tyrosine phosphorylated EphA2 interacts with the PTB and SH2 domains of SHC. We also show that the interaction of EphA2 with GRB2 is indirect and mediated by SHC and that this complex is necessary for EphA2-mediated activation of ERK kinases. These studies provide a novel mechanism to demonstrate how EphA2 can convey information from the cell exterior to the nucleus.
A trend in medical schools across the United States is the refurbishing of histology laboratories with digital microscopy systems. Although such systems may reduce curricular time, they do not teach basic microscope skills, and students who learn solely with these systems may be less prepared for their practices or specialties, particularly in rural areas that may not be equipped with digital microscope technology. At the West Virginia School of Osteopathic Medicine (WVSOM), students are trained to practice in a wide variety of environments, especially rural areas. A research survey was conducted to gather information for evidence-based decisions about histology education at WVSOM. The survey asked a range of questions concerning histology knowledge, tissue preparation, and microscopy. Responses did not differ significantly between physicians in urban versus rural practices. Ninety percent of physicians do not utilize digitized images, and only 50% have microscopes readily available. Regardless of the technology available, 90% feel that students must have microscope training and 88% of physicians feel that histology is important to the medical curriculum and use their histology knowledge often (weekly or daily) (66%). These results demonstrate that histology education should move toward a blending of traditional microscope and glass slides with computer-based instructional technologies.
The buzz about hyaluronan (HA) is real. Whether found in face cream to increase water volume loss and viscoelasticity or injected into the knee to restore the properties of synovial fluid, the impact of HA can be recognized in many disciplines from dermatology to orthopedics. HA is the most abundant polysaccharide of the extracellular matrix of connective tissues. HA can impact cell behavior in specific ways by binding cellular HA receptors, which can influence signals that facilitate cell survival, proliferation, adhesion, as well as migration. Characteristics of HA, such as its abundance in a variety of tissues and its responsiveness to chemical, mechanical and hormonal modifications, has made HA an attractive molecule for a wide range of applications. Despite being discovered over 80 years ago, its properties within the world of fascia have only recently received attention. Our fascial system penetrates and envelopes all organs, muscles, bones and nerve fibers, providing the body with a functional structure and an environment that enables all bodily systems to operate in an integrated manner. Recognized interactions between cells and their HA-rich extracellular microenvironment support the importance of studying the relationship between HA and the body’s fascial system. From fasciacytes to chronic pain, this review aims to highlight the connections between HA and fascial health.
Gross anatomy is a perennial source of anxiety for matriculating medical students due to a variety of factors, many of which could be considered "firsts," including: expectations to participate as a team member in the dissection laboratory; exposure to real human remains; and participating in a class composed predominantly of high-achieving students. In undergraduate medical education, prematriculation programs and courses are formal learning experiences designed for admitted students with the intention of fostering their social and emotional transition to medical school or to improve future academic performance (Heck et al., 2017); such programs may
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