• kinase
  • Its primary cellular target is the Bcr-Abl tyrosine kinase protein which is constitutively active and promotes the progression of CML. (drugbank.ca)
  • The T315I mutation confers resistance in cells as it prevents other Bcr-Abl inhibitors from binding to the Abl kinase. (drugbank.ca)
  • They also activate other kinase cascades. (embl.de)
  • These include serine/threonine kinases (Rho-kinase, Rho-associated coiled-coil-containing protein kinase, and protein kinase N), myosin phosphatase, and other novel proteins (rhophilin, rhotekin, and citron) (see Reference 2 2 for review). (ahajournals.org)
  • In addition to known regulators, two truncated forms of p21-activated kinase 2 (PAK2), PAK2ΔL 1-224 and PAK2ΔS 1-113 , both lacking the kinase domain, were isolated in the T cell screen. (jimmunol.org)
  • We show that this construct binds directly to the kinase domain of PAK2 and inhibits anti-TCR-stimulated T cell activation. (jimmunol.org)
  • For example, RAC and CDC42 share two protein serine-threonine kinase effectors in common, PAK and MLK, and inhibitors for both these kinases have been developed. (aacrjournals.org)
  • This domain can bind phosphatidylinositol lipids within biological membranes (such as phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate), and proteins such as the βγ-subunits of heterotrimeric G proteins, and protein kinase C. Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (wikipedia.org)
  • This is important because it makes the recruitment of different PH domain containing proteins sensitive to the activities of enzymes that either phosphorylate or dephosphorylate these sites on the inositol ring, such as phosphoinositide 3-kinase or PTEN, respectively. (wikipedia.org)
  • Proteins reported to contain PH domains belong to the following families: Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (wikipedia.org)
  • Other proteins known to bind RhoG in its GTP-bound state include the microtubule-associated protein kinectin, Phospholipase D1 and the MAP Kinase activator MLK3. (wikipedia.org)
  • FGD1 also activates the c-Jun N-terminal kinase (JNK) signaling cascade, important in cell differentiation and apoptosis. (wikipedia.org)
  • Cell Motility Mediated by Rho and Rho-Associated Protein Kinase Plays a Critical Role in Intrahepatic Metastasis of Human Hepatocellular Carcinoma. (wikipedia.org)
  • inhibit
  • To identify novel effectors downstream of the TCR, we designed a retroviral-based functional genetic screen to select for proteins that inhibit receptor-mediated T cell activation. (jimmunol.org)
  • pathways
  • The identification of molecular changes and aberrantly activated signaling pathways is, therefore, a prerequisite for the development of anticancer therapies targeting this specific breast cancer subtype. (aacrjournals.org)
  • RalA functions as a molecular switch to activate a number of biological processes, majorly cell division and transport, via signaling pathways. (wikipedia.org)
  • Qualitative analysis of induced proteins showed that enzymes linked to ROS production and scavenging were highly induced in control roots, while in MtROP9i the majority of proteins were involved in alternative defense pathways such as cell wall and protein degradation. (frontiersin.org)
  • Activated G proteins are able to couple to multiple downstream effectors and can therefore control a number of distinct signalling pathways (a characteristic known as pleiotropy). (wikipedia.org)
  • mammalian
  • Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell: the potential for multiplex signalling. (bio-rad.com)
  • RhoG-mediated Rac signalling has been shown to promote neurite outgrowth and cell migration in mammalian cells as well as phagocytosis of apoptotic cells in C. elegans. (wikipedia.org)
  • Many of the mammalian Dbl family proteins are tissue-specific and their number in Metazoa varies in proportion of cell signaling complexity. (wikipedia.org)
  • yeast
  • All eukaryote cells contain Rho GTPase (ranging from 6 in yeast to 20 in mammals). (wikipedia.org)
  • The CDC25 domain comprises approximately 500 amino acids and was first identified in the CDC25 protein in budding yeast Saccharomyces cerevisiae. (wikipedia.org)
  • effectors
  • While efforts continue to develop direct small GTPase inhibitors, a promising and more conventional therapeutic approach has been to block the activities of RHO GTPase effectors. (aacrjournals.org)
  • signalling pathway
  • Our results demonstrate an association between cognitive impairment and a defect in a signalling pathway that depends on a Ras-like GTPase. (embl.de)
  • activity
  • By enhancing their GTPase activity, GAP proteins inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might cause constitutive activation of their GTPase targets. (embl.de)
  • In particular, we propose that Arg 85 and Asn 194 are involved in binding G proteins and enhancing GTPase activity. (embl.de)
  • Rho GTPase-activating protein ( p200RhoGAP ) activity is stimulated by FYN oncogene related to SRC, FGR, YES ( Fyn ) phosphorylation [ 24 ]. (bio-rad.com)
  • Dock180, the archetypal member of this family, is seen as an atypical GEF in that efficient GEF activity requires the presence of the DOCK-binding protein ELMO (engulfment and cell motility) which binds RhoG at its N-terminus. (wikipedia.org)
  • GTPase activity of different mutant forms of p21, one cloned from a patient with myeloblastic leukaemia and one derived from in vitro mutagenesis, was measured. (wikipedia.org)
  • Results showed no correlation between the wild-type or mutant N-ras p21's GTPase activity and transforming potential. (wikipedia.org)
  • After size fractionation of FCS and analysis of the lipids that bound to serum albumin, the lysophosphatidic acid (LPA) was found to be responsible for the serum activity that induced stress fibre formation. (wikipedia.org)
  • The GEF activity of FGD1, which activates Cdc42, is harbored in its DH domain and causes the formation of filopodia, enabling the cells to migrate. (wikipedia.org)
  • PH domains are known to specifically bind to polyphosphoinositides and influence the enzymatic activity of the GEF they are located in. (wikipedia.org)
  • residues
  • The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. (abcam.com)
  • Residues conserved across the rhoGAP family are largely confined to one face of this bundle, which may be an interaction site for target G proteins. (embl.de)
  • Unlike Rho G-proteins, which undergo prenylation and methylation at their COOH-terminal cysteine residues, ARF6 undergoes myristoylation ( 1 , 2 ). (diabetesjournals.org)
  • The Ras GTPase-activating proteins are quite large (from 765 residues for sar1 to 3079 residues for IRA2) but share only a limited (about 250 residues) region of sequence similarity, referred to as the 'catalytic domain' or rasGAP domain. (wikipedia.org)
  • interaction
  • During vascular inflammation, neutrophils roll over the activated ECs through the interaction between selectins and their ligands, followed by adhesion to the ECs, which is mediated by the interaction between β2 integrins and ICAM-1 [ 1 ]. (pubmedcentralcanada.ca)
  • Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain of p190. (embl.de)
  • Together, such posttranslational modification steps have been proven to be essential for the targeting and association of these proteins with their membranous sites for optimal effector interaction ( 1 - 5 ). (diabetesjournals.org)
  • Another interaction partner of FGD1 is cortactin, which is directly bound by the proline-rich domain of FGD1. (wikipedia.org)
  • interact
  • Subsequently, activated αLβ2 and αMβ2 integrins interact with intercellular adhesion molecule-1 (ICAM-1) on the activated endothelium, thereby inducing neutrophil adhesion and crawling, respectively [ 2 , 3 ]. (pubmedcentralcanada.ca)
  • cell
  • The formation and maintenance of cell junctions and polarization are dependent on Rac and its hyperactivation disrupts epithelial architecture ( 5 ). (aacrjournals.org)
  • Recent intravital microscopic studies have provided compelling evidence that activated neutrophils adherent to inflamed ECs can support homotypic and heterotypic cell-cell interactions and that platelet-neutrophil aggregation on activated ECs is the crucial determinant of microvascular occlusion during vascular inflammation ( Fig. 1 ) [ 8 , 9 ]. (pubmedcentralcanada.ca)
  • Tissue and vascular injuries activate ECs, resulting in not only the expression of adhesion molecules including P-and E-selectins, ICAMs, and vascular cell adhesion mole-cule-1 (VCAM-1) but also the production and release of vWF, reactive oxygen species (ROS), and inflammatory cytokines [ 3 , 17 - 19 ]. (pubmedcentralcanada.ca)
  • Slit2 is cleaved into Slit2-N, a protein tightly binding to cell membranes, and Slit2-C, a diffusible fragment. (ahajournals.org)
  • Dimerization of Cool‐2 enables its Dbl ( d iffuse B ‐cell l ymphoma) and pleckstrin homology domains to work together ( in trans ) to bind specifically to Rac‐GDP. (embopress.org)
  • Thus, such enzymes exert a part of their effect on cell function by modulating the localization of downstream signaling proteins that possess PH domains that are capable of binding their phospholipid products. (wikipedia.org)
  • Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1). (wikipedia.org)
  • CED-12 (Cell Death Abnormality Protein-12) is a cytoplasmic, PH-domain containing adaptor protein found in Caenorhabditis elegans and Drosophila Melanogaster. (wikipedia.org)
  • CED-12 is an adaptor protein (proteins involved in facilitating the formation of signalling complexes) that is translated once apoptosis has been triggered in a cell. (wikipedia.org)
  • Apoptosis, also known as programmed cell death, activates during development as well as in situations where a cell has received sufficient physical damage. (wikipedia.org)
  • When receptors come in contact with cell surface markers on the apoptotic cell, a protein known as CED-6 (homolog for GULP in mammals) is expressed. (wikipedia.org)
  • Each Rho protein affects numerous proteins downstream, all of which having roles in various cell processes. (wikipedia.org)
  • Rho/Rac proteins are involved in a wide variety of cellular functions such as cell polarity, vesicular trafficking, the cell cycle and transcriptomal dynamics. (wikipedia.org)
  • Cell division control protein 42 homolog, also known as Cdc42, is a protein involved in regulation of the cell cycle. (wikipedia.org)