Michael Freeley

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Protein kinase C (PKC) is a family of serine/threonine kinases whose activity is controlled, in part, by phosphorylation on three conserved residues that are located on the catalytic domain of the enzyme, known as the activation-loop, the turn-motif, and the C-terminal hydrophobic-motif sites. Using a panel of phospho-specific antibodies, we have determined(More)
Chemokines such as SDF-1α play a crucial role in orchestrating T lymphocyte polarity and migration via polymerization and reorganization of the F-actin cytoskeleton, but the role of actin-associated proteins in this process is not well characterized. In this study, we have investigated a role for L-plastin, a leukocyte-specific F-actin-bundling protein, in(More)
The cell surface receptor CD44 is widely implicated in leukocyte migration to inflammatory sites. In this study, the responses of human T cells following cross-linking of CD44 were examined. We demonstrate that engagement of CD44 using immobilized mAbs or hyaluronan-enriched extracellular matrix lattices induces active migration in T lymphocytes accompanied(More)
We observe that protein kinase C (PKC) is phosphorylated on the activation loop at threonine 538 (Thr-538) before T cell activation. Our results are inconsistent with the conclusions of Lee et al. (Reports, 1 April 2005, p. 114) that the Thr-538 phosphorylation of PKC is regulated by T cell receptor activation. Other mechanisms, such as autophosphorylation(More)
RNA interfering (RNAi) screening strategies offer the potential to elucidate the signaling pathways that regulate integrin and adhesion receptor-mediated changes in T lymphocyte morphology. Of crucial importance, however, is the definition of key sets of parameters that will provide accurate, quantitative, and nonredundant information to flag relevant hits(More)
Protein kinase C θ (PKC θ) is a serine/ threonine kinase that is now firmly established as a central component in T cell activation , proliferation, differentiation, and apoptosis (Hayashi and Altman, 2007). Since it was first discovered that PKC θ re-localizes to the immunological syn-apse (IS) in conventional effector T cells following T cell stimulation,(More)
BACKGROUND & AIMS The ability of viruses to escape the host immune response represents a globally important problem related to a wide variety of pathogens. Hepatitis C is one of the major causes of liver disease worldwide. Clearance rates of this virus are low, and this condition normally involves a chronic inflammatory process. This raises a possibility(More)
Keynote address: " Marfan syndrome and related disorders: from gene to therapy " Prof. 3 AED Pregnancy register, UK and Ireland Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The risk magnitude varies by AED exposure. We provide results from the UK and Ireland Epilepsy and Pregnancy Registers,(More)
Thyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer-related deaths each year. Our group and others have previously demonstrated dysfunctional microRNA (miRNA or miR) expression in the context of thyroid cancer. The objective of the present study was to investigate the impact of synthetic manipulation of(More)
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