Paul A. Steimle

The broad goal of my research at UNCG is to gain further insight into how cells are able to achieve highly coordinated changes in shape that are required for critical cellular processes such as chemotaxis, cytokinesis, intracellular trafficking, and multicellular development. To this end, I use the social amoeba, Dictyostelium discoideum, as a model system for examining the molecular pathways regulating the ability of myosin II to mediate contraction of actin filaments in the highly dynamic context of a nonmuscle cell. More specifically, we have focused much of our attention on identifying factors that regulate the activity of an enzyme called myosin heavy chain kinase A (MHCK-A). MHCK-A plays a central role in regulating Dictyostelium cellular contraction by catalyzing the disassembly of myosin II filaments; the functional consequence of filament disassembly is the inactivation of myosin II-mediated contraction of the cell. The long term goal of my research program is to provide a clearer understanding of the molecular events driving cellular contractile processes since defects in the regulation of these events, as occur in cancer cells, can lead to uncontrolled cell multiplication (tumor formation) and unregulated cell migration observed with metastasis.

There are 14 included publications by Paul A. Steimle :

TitleDateViewsBrief Description
Actin-Activation of Myosin Heavy Chain Kinase A in Dictyostelium: A biochemical mechanism for the spatial regulation of myosin II filament disassembly 2005 1542 Studies in Dictyostelium discoideum have established that the cycle of myosin II bipolar filament assembly and disassembly controls the temporal and spatial localization of myosin II during critical cellular processes, such as cytokinesis and cell lo...
Galactosamine synthesizing enzymes are induced when Giardia encyst 1992 2195 Galactosamine, a Giardia filamentous cyst wall specific-sugar, is below the limits of detection in non-encysting trophozoites. Radiolabeling studies suggest that Giardia synthesize galactosamine primarily from endogenous glucose rather than salvage i...
Identification of a new mechanism for targeting myosin II heavy chain phosphorylation by Dictyostelium myosin heavy chain kinase B 2010 1984 Heavy chain phosphorylation plays a central role in regulating myosin II bipolar filament assembly in Dictyostelium, as well as in higher eukaryotic nonmuscle cells. Our previous work has demonstrated that the WDrepeat domain of Dictyostelium myosin ...
Lamellipodial localization of Dictyostelium myosin heavy chain kinase A is mediated via F-actin binding by the coiled-coil domain 2002 1631 Myosin heavy chain kinase A (MHCK A) modulates myosin II filament assembly in the amoeba Dictyostelium discoideum. MHCK A localization in vivo is dynamically regulated during chemotaxis, phagocytosis, and other polarized cell motility events, with pr...
Linking Ras to myosin function: RasGEF Q, a Dictyostelium exchange factor for RasB, affects myosin II functions 2008 2353 Ras guanine nucleotide exchange factor (GEF) Q, a nucleotide exchange factor from Dictyostelium discoideum , is a 143-kD protein containing RasGEF domains and a DEP domain. We show that RasGEF Q can bind to F-actin, has the potential to form compl...
Myosin heavy chain kinase A from Dictyostelium possesses a novel actin binding domain that cross-links actin filaments 2006 2260 Myosin heavy-chain kinase A (MHCK A) catalyses the disassembly of myosin II filaments in Dictyostelium cells via myosin II heavy-chain phosphorylation. MHCK A possesses a ‘coiled-coil’-enriched domain that mediates the oligomerization, cellular local...
Naringenin is a novel inhibitor of Dictyostelium cell proliferation and cell migration 2006 3586 Naringenin is a flavanone compound that alters critical cellular processes such as cell multiplication, glucose uptake, and mitochondrial activity. In this study, we used the social amoeba, Dictyostelium discoideum, as a model system for examining th...
A novel role for myosin II in insulin-stimulated glucose uptake in 3T3-L1 adipocytes 2005 2429 Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles from an intracellular pool to the plasma membrane. The studies presented here show that inhibition of my...
Polyphosphoinositides inhibit the interaction of vinculin with actin filaments 1999 2792 Binding of vinculin to adhesion plaque proteins is restricted by an intramolecular association of vinculin’s head and tail regions. Results of previous work suggest that polyphosphoinositides disrupt this interaction and thereby promote binding of vi...
Purification and characterization of encystment-induced glucosamine 6-phosphate isomerase in Giardia 1997 2853 Giardia intestinalis encystment results in the incorporation of galactosamine (GalN) (a cyst- wall specific sugar) into outer cyst wall filaments [1,2]. GalN is synthesized during encystment from endogenous glucose by an inducible enzyme pathway [3] ...
Recruitment of a myosin heavy chain kinase to actin-rich protrusions in Dictyostelium 2001 2263 Nonmuscle myosin II plays fundamental roles in cell body translocation during migration and is typically depleted or absent from actin-based cell protrusions such as lamellipodia, but the mechanisms preventing myosin II assembly in such structures ha...
Specific phosphorylation of threonine by the Dictyostelium myosin II heavy chain kinase family 2001 1586 Dictyostelium myosin II heavy chain kinase A (MHCK A), MHCK B, and MHCK C contain a novel type of protein kinase catalytic domain that displays no sequence identity to the catalytic domain present in conventional serine, threonine, and/or tyrosine pr...
WD Repeat Domain of Dictyostelium Myosin Heavy Chain Kinase C Functions in both Substrate Targeting and Cellular Localization 2010 1882 Myosin II disassembly in Dictyostelium discoideum is regulated by three structurally related myosin heavy chain kinases (myosin II heavy chain kinase A [MHCK-A], -B, and -C). We show that the WD repeat domain of MHCK-C is unique in that it mediates b...
WD-Repeat domains target Dictyostelium myosin heavy chain kinase activities by binding directly to myosin II 2000 1334 Myosin heavy chain kinase (MHCK) A phosphorylates mapped sites at the C-terminal tail of Dictyostelium myosin II heavy chain, driving disassembly of myosin filaments both in vitro and in vivo. MHCK A is organized into three functional domains that in...