Actin polymerization polymerizing protein

SARA is a scaffolding protein that regulates the subcellular localization of inactivated R-Smads, potentially scaffolding the TGF-P receptor kinase to the Smad 2 substrate. Filamins are a family of actin polymerization proteins that also form scaffolds for a range of signaling proteins including SAP kinases such as MKK-4, small GTPases Rho and Ras, as well as Smad 2 and Smad 5. 

Nonmuscle Actin-Binding Proteins Drugs Affecting Actin Polymerization Patterns of Arrangement of Actin Filaments in Animal Cells Three-Dimensional Networks The Microtrabecular Lattice... 

Proteins that bind to actin monomers and inhibit polymerization are designated as profilins (12—15 kD) (Sun et al., 1995). In addition to functioning as an actin-monomer-sequestering protein, profilin binds at least three other... 

Actin Polymerization Regulation by Divalent Metal Ion and Nucleotide Bindings ATP Hydrolysis and Actin Binding Proteins... 

Actin is a 42 kDa bent dumbbell-shaped globular monomer which is found in most eukaryotic cells. It is the primary protein of the thin (or actin) filaments. Also, by mass or molarity, actin is the largest constituent of the contractile apparatus, actually reaching millimolar concentrations. Actins from different sources seem to be more similar than myosins from the same sources. Actin binds ATP which is hydrolyzed to ADP, if the monomeric actin polymerizes. The backbone structure of the actin filament is a helix formed by two linear strands of polymerized actins like two strings of actin beads entwined. 

Monomeric G-actin (43 kDa G, globular) makes up 25% of muscle protein by weight. At physiologic ionic strength and in the presence of Mg, G-actin polymerizes noncovalently to form an insoluble double helical filament called F-actin (Figure 49-3). The F-actin fiber is 6-7 nm thick and has a pitch or repeating structure every 35.5 nm. 

C terminus (ILWEQ), WASp homology 2 (WH2), profilin (PROF), and cyclase-associated protein, domains are all present in fungi, plants, and metazoa. Many of these domains bind similar sites on actin, although they possess different properties with respect to actin polymerization (reviewed in Van Troys et al., 1999). 

Figure 2 The actin-ADP-ribosylating toxins, (a) Molecular mode of action. The actin-ADP-ribosylating toxins covalently transfer an ADP-ribose moiety from NAD+ onto Arg177 of G-actin in the cytosol of targeted cells. Mono-ADP-ribosylated G-actin acts as a capping protein and inhibits the assembly of nonmodified actin into filaments. Thus, actin polymerization is blocked at the fast-growing ends of actin filaments (plus or barbed ends) but not at the slow growing ends (minus or pointed ends). This effect ultimately increases the critical concentration necessary for actin polymerization and tends to depolymerize F-actin. Finally, all actin within an intoxicated cell becomes trapped as ADP-ribosylated G-actin.

The principal cytoskeletal proteins in non-muscle cells are actin, tubulin, and the components of intermediate filaments. Actin can exist either as monomers ( G-actin ) or polymerized into 70 A diameter double filament ( F-actin ). Polymerized actin usually is localized at the margins of the cells, linked by other proteins to the cell membrane. In contrast, tubulin forms hollow filaments, approximately 250 A in diameter, that are distributed within a cell in association, generally, with cell organelles. Stabilized microtubule structures are found in the flagella and cilia of eucaryotic cells however, in other instances - examples being the mitotic apparatus and the cytoskeletal elements arising in directed cell locomotion - the microtubules are temporal entities. Intermediate filaments, which are composed of keratin-like proteins, are approximately 100 A thick and form stable structural elements that impart rigidity, for example, to nerve axons and epithelial cells. 

The work that follows pertains primarily to actin networks. Many proteins within a cell are known to associate with actin. Among these are molecules which can initiate or terminate polymerization, intercalate with and cut chains, crosslink or bundle filaments, or induce network contraction (i.e., myosin) (A,11,12). The central concern of this paper is an exploration of the way that such molecular species interact to form complex networks. Ultimately we wish to elucidate the biophysical linkages between molecular properties and cellular function (like locomotion and shape differentiation) in which cytoskeletal structures are essential attributes. Here, however, we examine the iri vitro formation of cytoplasmic gels, with an emphasis on delineating quantitative assays for network constituents. Specific attention is given to gel volume assays, determinations of gelation times, and elasticity measurements. 

In the absence of a sequestering protein, actin polymerization will proceed to equilibrium or it will reach a steady-state extent of polymerization, at which point d[Apoiy]/dt = 0. [A] 00 is the critical concentration, equal to kJk+. In the presence of a sequestering protein, [Atotai] = [Afree] + [Apoiy] + [AX], and after polymerization reaches equilibrium, the unpolymerized actin concentration [A]oo will equal [AX ] + [Afree]. Hence,... 

Symons, M., Derry, J. M. J., Karlak, B., etal, Wiskott-Aldrich syndrome protein, anovel effector for the GTPase CDC42HS, is implicated in actin polymerization. Cell 84, 723-734 (1996). 

Polymerization and depolymerization of actin, the main component of microfilaments, is controlled by a series of proteins, the activity of which is controlled by Ca and/or Ptdlns(4,5)P2. The Ca regulated proteins (see 6.7) are chiefly involved in processes of depolymerization of actin. Many of the proteins involved in the opposite process, actin polymerization, have specific binding sites for PtdIns(4,5)P2 and Ptlns(4)P and are regulated by the availability of phosphoinositides. Examples of such proteins are profilin, gelsolin, villin and talin (review Janmey, 1994). 

Actin is a protein that polymerizes at physiologic ionic strength levels into thin filaments. The monomers in actin are oriented to one another by a rotation of 166° and a translation of 275 nm. This gives an assembly that resembles a double-stranded string of beads. 

Cellular Activation. Chemokines are potent cell activators after binding to the appropriate G protein-linked, seven-transmembrane spanning receptors, chemokines elicit transient intracellular calcium flux, actin polymerization, oxidative burst with release of superoxide free radicals, exocytosis of secondary granule constituents, and increased avidity of integrins for their adhesion molecules (Dl, E2). 

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