Anne J Ridley

..These results indicate that HGF stimulates PAK4 through PI3K, and that PAK4 could contribute to HGF-induced changes in actin organisation and cell-substratum adhesion...

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..Since macrophages do not express RhoC, these effects of C3 transferase are due to inhibition of RhoA rather than RhoB. Our results suggest that RhoB affects cell shape and migration by regulating surface integrin levels...

..This work identifies the RhoA/ROCK pathway as a major target of p110delta-mediated PI3K signalling, and establishes for the first time that PI3K controls itself, via a feedback loop involving PTEN...

..These results suggest that the gradual increase in permeability induced by TNF-alpha does not reflect contractile mechanisms mediated by Rho, ROCK, and MLCK, but involves long-term reorganization of tight junction proteins...

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..These results indicate that dimerization via the N-terminus is critical for ROCK-I function in cells and for its regulation by RhoE...

..Rho GTPases are therefore candidate targets for inhibiting leukocyte transendothelial migration in heart disease and chronic inflammatory disorders...

..Together, these data show that Rac1 and Rac2 have distinct roles in regulating cell morphology, migration and invasion, but are not essential for macrophage migration or chemotaxis...

..Taken together, these findings suggest that PI3KC2beta regulates the migration and survival of human tumor cells by distinct molecular mechanisms...

..Finally, we describe how to image and quantitate leukocyte TEM by digital time-lapse microscopy...

..This is the first demonstration of an endogenous Rho family member being phosphorylated in vivo and indicates that phosphorylation is an important mechanism to control the stability and function of this GTPase-deficient Rho protein...

..These data suggest that RhoE induces stress fiber disassembly by directly binding ROCK I and inhibiting it from phosphorylating downstream targets...

..These results suggest that ERM proteins are required for microvillar positioning of L-selectin and that this is important both for leukocyte tethering and L-selectin shedding...

..Together, these data indicate that PAK1 signals via ERK1/2 to regulate lamellipodial stability...

..RhoE itself is phosphorylated by ROCK I, and this may enhance RhoE regulation of ROCK I function. This chapter describes the method used for studying ROCK inhibition by RhoE...

..Our results suggest that the migration speed of macrophages is regulated independently of spread area or membrane ruffling and that Vav1 is selectively required to maintain a normal migration speed...

..RhoE also inhibited Ras- and Raf-induced fibroblast transformation. These results indicate that RhoE inhibits cell cycle progression upstream of the pRb checkpoint...

..We therefore propose that binding of p120ctn to microtubules is inversely related to its ability to regulate Rho GTPases...

..These data identify CKI epsilon as a novel occludin kinase that may be important for the regulation of occludin...

..A recent meeting at the Max Delbrück Center in Berlin, Germany provided a forum to discuss the molecular mechanisms of cell migration in a broad range of contexts including chemotaxis, development, immunity, and cancer...

..These results indicate that in endothelial cells, ICAM-1, but not ICAM-2, rapidly stimulates signaling responses involving RhoA...

..Our findings demonstrate that p110beta is the major class I catalytic isoform required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by primary macrophages...

..Recent experiments have defined new functions of ROCKs in cells, including centrosome positioning and cell-size regulation, which might contribute to various physiological and pathological states...

..We also discuss strategies for targeting Rho GTPase signalling in therapies for diseases involving altered endothelial permeability...

..Our results show that endothelial cells reorient in response to shear stress by a two-step process involving Rho-induced depolarization, followed by Rho/Rac-mediated polarization and migration in the direction of flow...

..We propose that phosphorylation of Tyr(291) directly regulates WASp function...

..Here, we describe the procedure for microinjecting cells with purified recombinant proteins or with expression vectors encoding proteins, and for analyzing the cells after injection...

..However, Rac1-deficient macrophages show normal migration and chemotaxis. Thus in macrophages Rac1 is primarily responsible for regulating cell morphology, contributes to membrane ruffling, but is not required for migration...

..We propose that constitutive VCA domain phosphorylation is required for optimal stimulation of the Arp2/3 complex by WASP...

..This review discusses recent findings on ERM protein function in leucocytes and how these may be integrated with Rho GTPase signalling...

..Our results indicate that CSF-1 acts via PI 3-kinase to enhance podosome assembly and that this is linked to macrophage polarization...

..Giannone and coworkers (this issue of Cell) describe how cells periodically pull back on these protrusions in order to sense and respond to the rigidity of their environment...

..In this review, we discuss recent findings on leucocyte-induced alterations to endothelial cells, and the roles of Rho GTPases in these responses...

..In cancer cells, the expression and activity of RhoA, B, and C is altered in different ways. Together, this evidence suggests that although the 3 isoforms of Rho are structurally highly homologous, they have different cellular functions...

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..However, there is little evidence so far from animal studies to define if and how Rho proteins contribute to cancer cell proliferation, survival, invasion and metastasis...

..Thus, RhoE is anticipated to function by regulating ROCK I signaling to control the balance between cell survival and cell death in response to genotoxic stress...

..These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis...

..DC therefore coordinate adhesion and protrusion to perform a specialized process of cellular morphogenesis, which differentiates these cells from all other cells of the immune system and may contribute to their distinctive function...

..These observations have direct implications for the clearance of dying cells and the roles played by different phagocytes in antigen digestion and presentation...

..These data show that acute hypoxia induces RhoA activation only in PASMCs from young animals, whereas chronic hypoxia selectively downregulates RhoA activity in outer medial PASMCs leading to an altered phenotype...

..The unusual combination of a dendritic morphology and high motility is likely to play a major role in the efficient function of DCs as sentinels of the immune system...

..Moreover, invasion mediated by constitutively active Cdc42 was attenuated by IQGAP1DeltaGRD. Thus, IQGAP1 has a fundamental role in cell motility and invasion...

..Our findings suggest that PSKs form a subgroup of sterile 20 (STE20)-like kinases that regulate different cytoskeletal processes...

..The recent availability of knockout mice for several members of the Rho family reveals new information about their roles in signalling to the cytoskeleton and in development...

..Our results thus demonstrate a chemokine-specific signaling pathway in which Gi and PI3Kgamma coordinate to drive Rac1 and PAK2 activation that eventually controls the chemotactic response...

..Here, we discuss how Rho GTPases could contribute to different steps of cancer progression, including proliferation, survival, invasion and metastasis...

..These observations suggest that pharmacological targeting of p110delta activity is a viable strategy for the therapy of T cell-mediated pathology...

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..By superposition of the RhoE structure on structures of Rho family proteins in complex with binding partners, we make predictions on RhoE interactions with these partners...

..These results reveal embryo-induced and localized endometrial responses that may govern implantation of the human embryo...

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..Taken together, these results suggest that amphoterin binds to RAGE through a COOH-terminal motif that can be used as an efficient inhibitor to block invasive migration of tumor cells...

..These results demonstrate that PSK interacts with microtubules and affects their organization and stability independently of PSK kinase activity...

..Our findings identify a novel pathway regulating angiogenesis through ICAM-2 and a novel mechanism for Rac activation during angiogenesis...

..These results indicate that the initial actin reorganization induced by either a GPCR or tyrosine kinase receptor agonist is not dependent on PI3Kgamma, whereas PI3Kgamma is needed for optimal migration of macrophages to either agonist...

..This is a particularly useful protocol as it can be adapted to study bone marrow-derived macrophages isolated from genetically modified mice and thus study the requirement for a specific protein in cell migration and chemotaxis...