PKCα and PKCδ Regulate ADAM17-Mediated Ectodomain Shedding of Heparin Binding-EGF through Separate Pathways

Epidermal growth factor receptor (EGFR) signalling is initiated by the release of EGFR-ligands from membrane-anchored precursors, a process termed ectodomain shedding. This proteolytic event, mainly executed by A Disintegrin And Metalloproteases (ADAMs), is regulated by a number of signal transduction pathways, most notably those involving protein kinase C (PKC). However, the molecular mechanisms of PKC-dependent ectodomain shedding of EGFR-ligands, including the involvement of specific PKC isoforms and possible functional redundancy, are poorly understood. To address this issue, we employed a cell-based system of PMA-induced PKC activation coupled with shedding of heparin binding (HB)-EGF. In agreement with previous studies, we demonstrated that PMA triggers a rapid ADAM17-mediated release of HB-EGF. However, PMA-treatment also results in a protease-independent loss of cell surface HB-EGF. We identified PKCα as the key participant in the activation of ADAM17 and suggest that it acts in parallel with a pathway linking PKCδ and ERK activity. While PKCα specifically regulated PMA-induced shedding, PKCδ and ERK influenced both constitutive and inducible shedding by apparently affecting the level of HB-EGF on the cell surface. Together, these findings indicate the existence of multiple modes of regulation controlling EGFR-ligand availability and subsequent EGFR signal transduction

Commitment Decisions Under the Polish Competition Act – Enforcement Practice and Future Perspectives

The aim of this paper is to provide an analysis of the commitments procedure under the Polish competition law, including both legal and economic perspective. The outcome of this research is supposed to help in estimation whether novel negotiated instruments may be successfully employed in the field of antitrust enforcement. Hence, the paper first introduces the legal background of the commitments decisions, with focus on the specific features of the procedure. Being a tool of antitrust enforcement, commitment decisions should contribute to its goals. Therefore, the paper identifies such objectives drawing on the economic literature. It is in the light of these criteria that the decision practice of the Polish competition authority, still in the stage of development, is subsequently evaluated. This assessment reveals circumstances, under which the competition authority is particularly apt to engage into commitments procedure. It allows also for a conclusion that the application of this negotiated instrument is in principle commensurate with the exigencies following from economic theory.Le but de cet article est de présenter une analyse de la procédure d’engagements en droit polonais de la concurrence, d’un point de vue juridique et économique. Le résultat de cette recherche permettra d’estimer l’efficacité de ces nouvelles procédures négociées dans le domaine du droit de la concurrence. Ainsi, l’article introduit le cadre juridique de la procédured’engagements en Pologne, en se focalisant sur les éléments spécifiques d’un tel mécanisme. Instrument de mise en œuvre du droit de la concurrence, la procédure d’engagements devrait contribuer à accomplir les buts de cette politique. Par conséquent, l’article essaie d’identifier de tels objectifs, en s’appuyant sur la littérature économique. La pratique décisionnelle de l’autorité de la concurrence polonaise est par la suite analysée à la lumière de ces critères, tout en gardant à l’esprit qu’elle n’en est qu’à ses prémisses. Cette analyse revèle les circonstances dans lesquelles l’autorité de la concurrence est particulièrement susceptible de mettre en œuvre une procédure d’engagements. Elle nous permet aussi de constater que l’application des procédures négociées en Pologne est, en principe, conforme aux exigences relevant de la théorie économique. Néanmoins, quelques suggestions visant à l’amélioration de la procédure d’engagements sont proposées, au cas où cela soit nécessaire

Myosin XIX.” In Myosins: A Superfamily of Molecular Motors

The birth of widely available genomic databases at the turn of the millennium led to the identification of many previously unknown myosin genes and identification of novel classes of myosin, including MYO19. Further sequence analysis has revealed the unique evolutionary history of class XIX myosins. MYO19 is found in species ranging from vertebrates to some unicellular organisms, while it has been lost from some lineages containing traditional experimental model organisms. Unique sequences in the motor domain suggest class-specific mechanochemistry that may relate to its cellular function as a mitochondria-associated motor. Work over the past 10 years has demonstrated that MYO19 is an actin-activated ATPase capable of actin-based transport, and investigation of some of the conserved differences within the motor domain indicate their importance in MYO19 motor activity. The cargo-binding MyMOMA tail domain contains two distinct mechanisms of interaction with mitochondrial outer membrane components, and perturbation of MYO19 expression leads to alterations in mitochondrial movement and dynamics that impact cell function. This chapter summarizes the current state of the field and highlights potential new directions of inquiry

Secretome Signature of Invasive Glioblastoma Multiforme

The incurability of malignant glioblastomas is mainly attributed to their highly invasive nature coupled with resistance to chemo- and radiation therapy. Because invasiveness is partially dictated by the proteins these tumors secrete we used SILAC to characterize the secretomes of four glioblastoma cell lines (LN18, T98, U118 and U87). Although U87 and U118 cells both secreted high levels of well-known invasion promoting proteins, a Matrigel invasion assay showed U87 cells to be eight times more invasive than U118 cells, suggesting that additional proteins secreted by U87 cells may contribute to the highly invasive phenotype. Indeed, we identified a number of proteins highly or exclusively expressed by U87 cells as compared to the less invasive cell lines. The most striking of these include ADAM9, ADAM10, cathepsin B, cathepsin L1, osteopontin, neuropilin-1, semaphorin-7A, suprabasin and chitinase-3-like protein 1. U87 cells also expressed significantly low levels of some cell adhesion proteins such as periostin and EMILIN-1. Correlation of secretome profiles with relative levels of invasiveness using Pavlidis template matching further indicated potential roles for these proteins in U87 glioblastoma invasion. Antibody inhibition of CH3L1 reduced U87 cell invasiveness by 30%

Państwo demokratyczne, prawne i socjalne: księga jubileuszowa dedykowana profesorowi Zbigniewowi Antoniemu Maciągowi. T. 3, Studia prawne

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