... engagement triggers rapid GTP-loading of the small GTPase Rac as a master regulator of cytoskeletal rearrangements and lamellipodia-driven internalization. To identify components of the CEACAM3-initiated signaling cascade, we performed a genome-wide CRISPR/Cas9-based screen in human myeloid cells. Following...

...Frieda Kage; Hermann Döring; Magdalena Mietkowska; Matthias Schaks; Franziska Grüner; Stephanie Stahnke; Anika Steffen; Mathias Müsken; Theresia E. B. Stradal; Klemens Rottner ABSTRACT Cell migration frequently involves the formation of lamellipodia induced by Rac GTPases activating WAVE regulatory...

... upregulates lamellipodin expression. This is mediated by an integrin-dependent FAK–Cas–Rac signaling module and supports stiffness-mediated lamellipodin induction. Mechanistically, we find that lamellipodin overexpression increased, and lamellipodin knockdown reduced, stiffness-induced cell cyclin expression...

... neutrophil-like cells display disrupted mitochondria–ER interaction, heightened intracellular Ca 2+ levels and elevated Rac activation after chemokine stimulation. Restoring a mitochondria–ER tether rescues the abnormal Ca 2+ levels, Rac hyperactivation and chemotaxis defect resulting from MFN2 depletion...

..., phagocytosis, and macropinocytosis . Physiol. Rev.   93 , 69 - 106 . 10.1152/physrev.00002.2012 Bokoch , G. M. , Vlahos , C. J. , Wang , Y. , Knaus , U. G. and Traynor-Kaplan , A. E. ( 1996 ). Rac GTPase interacts specifically with phosphatidylinositol 3-kinase . Biochem. J...

... to these processes are complex. Here, we modify the activity of the two Rho GTPase family members Rac and Cdc42 by optogenetically recruiting specific guanine nucleotide exchange factor (GEF) DH or PH domains to defined regions of the cell membrane. We find that the localized activation of both GTPases produces...

.... Once activated, RAS-GTP binds to and activates a spectrum of downstream effectors with distinct catalytic functions (see Box 1 ). GTPase Oncogene PI3K Rac Raf Ral Summary: In this Cell Science at a Glance article, we discuss the distinct roles of and properties of RAS isoforms...

...Shinichiro Nakahara; Koji Tsutsumi; Takuya Zuinen; Yasutaka Ohta ABSTRACT Rho family small GTPases are essential for the formation of adherens junctions in epithelial cells. Here, we found that FilGAP (also known as ARHGAP24), a Rac-specific Rho GTPase-activating protein, promoted the formation...

... that Rac1 translocates to the membrane at domain boundaries, then diffuses into raft and non-raft domains, which controls interactions. These findings resolve discrepancies in our understanding of Rac biology and identify novel mechanisms by which lipid rafts modulate Rho GTPase signaling. * Present...

... that the spatially controlled activation of receptor tyrosine kinases (RTKs) by guidance cues limits Rac activity at the leading edge, which is crucial for establishing and maintaining polarized cell protrusions at the front. However, little is known about the mechanisms by which RTKs control the local activation...

...Monica Croke; F. Patrick Ross; Matti Korhonen; David A. Williams; Wei Zou; Steven L. Teitelbaum Cdc42 mediates bone resorption principally by stimulating osteoclastogenesis. Whether its sister GTPase, Rac, meaningfully impacts upon the osteoclast and, if so, by what means, is unclear. We find...

... neurite retraction in both N1E-115 cells and cerebellar granule neurones. However, how PIP5Ks are regulated or how they induce neurite retraction is not well defined. Here, we show that neurite retraction induced by PIP5Kβ is dependent on its interaction with the low molecular weight G protein Rac. We...

... or Rac pull-down assays in HeLa cells, where, in common with full-length protein, δ-catenin ΔARM1-5 inhibits Rho while activating Rac ( supplementary material Fig. S5C ,D). Notably, δ-catenin ΔARM1-5 showed only weak rescue effects following δ-catenin depletion compared with the full-length construct...

... and metastasis through its dual actin-bundling and active PKC-binding activities. Rac was implicated as a regulator of fascin-dependent colon carcinoma cell migration in vitro. Here, we tested the hypothesis that Rac regulates the interaction of fascin with active PKC. The major conventional PKC in colon...

...Wassim Abou-Kheir; Beth Isaac; Hideki Yamaguchi; Dianne Cox Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous (WAVE) proteins play a major role in Rac-induced actin dynamics, but Rac does not bind directly to WAVE proteins. It has been proposed that either the insulin receptor...

... the stroma can influence tumor behavior by regulating the tissue phenotype, we explored the role of extracellular matrix signaling and tissue organization in epithelial survival. We report that elevated (α6)β4 integrin-dependent Rac-Pak1 signaling supports resistance to apoptosis in mammary acini...

... phosphoinositide 3-kinases (PI 3-kinases). Both Rac and Ras have been shown to regulate actin polymerization and activate PI 3-kinase. However, the coordination of Rac, Ras and PI 3-kinase activation during epidermal growth factor (EGF)-stimulated protrusion has not been analyzed. We examined PI 3-kinase-dependent...

... stress Laminin α6β4 integrin Rac PI 3-kinase Cell cycle The effects of mechanical force induced by fluid shear stress on the activity of several signal transduction pathways in endothelial cells is well documented (for a review, see Resnick and Gimbrone, Jr, 1995 ). Mechanical forces...

... important process. * Author for correspondence (e-mail: ravi@virginia.edu ) 19 4 2007 © The Company of Biologists Limited 2007 2007 Engulfment Apoptosis GULP ELMO Doc 180 Rac C. elegans Programmed cell death (apoptosis) represents a multi-step process...

... sheath of hair follicles, we generated transgenic mice expressing a dominant inhibitory mutant of Rac, N17Rac1, under the control of the keratin 14 promoter. These mice do not exhibit an overt skin phenotype but show protracted skin wound re-epithelialization. Investigation into the underlying mechanisms...