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Small G Proteins (small + g_protein)
Selected AbstractsZoledronate has an antitumor effect and induces actin rearrangement in dexamethasone-resistant myeloma cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2007Masayuki Koizumi Abstract New strategies are needed to overcome the resistance of multiple myeloma (MM) to dexamethasone (Dex). Several recent in vitro studies demonstrated the antitumor effect of nitrogen-containing amino-bisphosphonates (N-BPs) in various tumor cell lines. Inhibition of the prenylation of small G proteins is assumed to be one of the principal mechanisms by which N-BPs exert their effects. There have been few reports on N-BP treatment of MM cells that are resistant to Dex. Additionally, it is not known how small G proteins are altered in N-BP-treated MM cells. In this study, we evaluated the effect of the most potent N-BP, zoledronate (ZOL), on a Dex-resistant human MM cell subline (Dex-R) that we established from the well-documented RPMI8226 cell line. ZOL reduced the viability and induced apoptosis of Dex-R cells. Some of the ZOL-treated RPMI8226 cells and ZOL-treated Dex-R cells were elongated; however, elongated cells were not seen among the Dex-treated RPMI8226 cells. Furthermore, we found that portions of the small G proteins, Rho and Rap1A, were unprenylated in the ZOL-treated MM cells. Geranylgeraniol reduced the above-mentioned ZOL-induced effects. These findings suggest that ZOL may be beneficial for the treatment of Dex-resistant MM by suppressing the processing of RhoA and Rap1A. [source] ERK activation by mechanical strain is regulated by the small G proteins rac-1 and rhoAEXPERIMENTAL DERMATOLOGY, Issue 2 2004Julien Laboureau Abstract: Physical forces play an important role in regulating cell functions. We applied mechanical strain to human fibroblasts by magnetic attraction of superparamagnetic arginine-glycine-aspartic acid (RGD)-coated beads. We confirmed that the MAP kinases Erk and p38 are activated by mechanical strain, and went further by demonstrating the activation of Elk-1 by mechanical strain, mainly through a MEK-Erk pathway. Transfection of a dominant negative form of the G protein rac-1 (rac T17N), and inhibition of PI3K, an effector of rac-1, efficiently prevented Elk-1 activation by mechanical forces. Transfection with C3 transferase, known to inhibit rhoA, and inhibition of rock (a downstream effector of rhoA), gave similar results. However, contrary to the active form of rhoA (rho G14V), transfection of the active form of rac-1 (rac G12V) induced Elk activation and mimicked the effects of mechanical strain. These results point out that the two small G proteins rhoA and rac-1 participate in cell sensitivity to mechanical strain and lead to the modulation of the Erk pathway. [source] Involvement of Cdc42 and Rac small G proteins in invadopodia formation of RPMI7951 cellsGENES TO CELLS, Issue 12 2003Hirokazu Nakahara Background:, Invadopodia are membrane protrusions into the extracellular matrix by aggressive tumour cells. These structures are associated with sites of matrix degradation and invasiveness of malignant tumour cells in an in vitro fibronectin degradation/invasion assay. The Rho family small G proteins, consisting of the Rho, Rac and Cdc42 subfamilies, are implicated in various cell functions, such as cell shape change, adhesion, and motility, through reorganization of the actin cytoskeleton. We studied the roles of the Rho family small G proteins in invadopodia formation. Results:, We first demonstrated that invadopodia of RPMI7951 human melanoma cells extended into the matrix substratum on a vertical view using a laser scanning confocal microscope system. We confirmed that invadopodia were rich in actin filaments (F-actin) and visualized clearly with F-actin staining on a vertical view as well as on a horizontal view. We then studied the roles of Rho, Rac, and Cdc42 in invasiveness of the same cell line. In the in vitro fibronectin degradation/invasion assay, a dominant active mutant of Cdc42 enhanced dot-like degradation, whereas a dominant active mutant of Rac enhanced diffuse-type degradation. Furthermore, frabin, a GDP/GTP exchange protein for Cdc42 with F-actin-binding activity, enhanced both dot-like and diffuse-type degradation. However, a dominant active mutant of Rho did not affect the fibronectin degradation. Moreover, inhibition of phosphatidylinositol-3 kinase (PI3K) disrupted the Rac and Cdc42-dependent actin structures and blocked the fibronectin degradation. Conclusion:, These results suggest that Cdc42 and Rac play important roles in fibronectin degradation and invasiveness in a coordinate manner through the frabin-Cdc42/Rac-PI3K signalling pathway. [source] Nectins and nectin-like molecules: Roles in cell adhesion, migration, and polarizationCANCER SCIENCE, Issue 8 2003Yoshimi Takai Nectins are a family of Ca2+ -independent immunoglobulin-like cell-cell adhesion molecules consisting of four members, which homophilically and heterophilically trans-interact and cause cell-cell adhesion. Nectin-based cell-cell adhesion is involved in the formation of cadherin-based adherens junctions in epithelial cells and fibroblasts. The nectin-based cell-cell adhesion induces activation of Cdc42 and Rac small G proteins, which eventually regulate the formation of adherens junctions through reorganization of the actin cytoskeleton, gene expression through activation of a mitogen-activated protein kinase cascade, and cell polarization through cell polarity proteins. Five nectin-like molecules (necls), which have domain structures similar to those of nectins, have recently been identified and appear to play different roles from those of nectins. One of them, named necl-5, which does not homophilically trans -interact, but heterophilically trans -interacts with nectin-3, regulates cell migration and adhesion. In this article, the roles and modes of action of nectins and necls in cell adhesion, migration, and polarization are reviewed. [source] | ||||||||||