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  • CDC42
  • The three best studied members of the RHO family, RAC1, CDC42, and RHOA, are essential for transformation by activated RAS ( 3, 4 ), and, in the case of RAC1 and RAC2, themselves can be oncogenic drivers in human malignancies ( 5, 6 ). (aacrjournals.org)
  • CDC42 also has distinct kinase effectors, such as MRCK and the tyrosine kinase ACK, and these kinases too might provide suitable drug targets in cancer. (aacrjournals.org)
  • The three major RHO-family GTPases, CDC42, RAC, and RHO, are activated by guanine-nucleotide exchange factors (GEF), which are in turn regulated by signals originating at the cell surface. (aacrjournals.org)
  • CDC42 encodes a highly conserved GTPase of the Rho family that is best known for its role in regulating cell polarity and actin organization. (asm.org)
  • Furthermore, the ste20 Δ CRIB allele, previously used to disrupt the Cdc42p-Ste20p interaction, behaved as an activated allele, largely bypassing the signaling defect of the cdc42 mutants. (asm.org)
  • Overexpression of AND-34 in murine B cell lines activates the Rho family GTPase Cdc42, but not Rac, Rho, RalA, or Rap1. (jimmunol.org)
  • These studies suggest that p130Cas and HEF1-associated AND-34 may regulate B cell adhesion and motility through a Cdc42-mediated signaling pathway. (jimmunol.org)
  • X-ray crystallography reveals the molecular nature of the interaction between PAK4 and CDC42 and shows that in addition to the canonical PAK4 CDC42/RAC interactive binding (CRIB) domain binding to CDC42 there are unexpected contacts involving the PAK4 kinase C-lobe, CDC42, and the PAK4 polybasic region. (pnas.org)
  • These additional interactions modulate kinase activity and increase the binding affinity of CDC42 for full-length PAK4 compared with the CRIB domain alone. (pnas.org)
  • We therefore show that the interaction of CDC42 with PAK4 can influence kinase activity in a previously unappreciated manner. (pnas.org)
  • The apical localization of Mbt was cell cycle dependent and regulated by binding to Cdc42, which is essential for Mbt function in neuroblasts. (uni-wuerzburg.de)
  • phosphatidylinositol 3-kina
  • The present study reveals a dual and specific role of phosphatidylinositol 3-kinase (PI3K) in IL-2R endocytosis. (biologists.org)
  • Increased phosphatidylinositol 3-kinase (PI3K) and AKT or decreased PTEN activity in prostate cancer cells also increases HIF-1α expression by an undefined mechanism. (asm.org)
  • receptor
  • In breast cancer, increased activity of the HER2 (also known as neu) receptor tyrosine kinase is associated with increased tumor grade, chemotherapy resistance, and decreased patient survival. (asm.org)
  • HIF-1 activates the transcription of genes whose products are required for critical aspects of tumor progression including angiogenesis (plasminogen activator inhibitor 1 and VEGF), iron homeostasis (transferrin and transferrin receptor), and metabolic adaptation (glucose transporters and glycolytic enzymes), as well as several factors that affect tumor cell survival or proliferation (endothelin 1, inducible nitric oxide synthase, and insulin-like growth factor 2). (asm.org)
  • PI3K
  • 6 In response to shear stress, this complex stimulates phosphoinositide 3-kinase (PI3K), which then leads to integrin activation. (ahajournals.org)
  • Here we demonstrate that HER2 signaling induced by overexpression in mouse 3T3 cells or heregulin stimulation of human MCF-7 breast cancer cells results in increased HIF-1α protein and VEGF mRNA expression that is dependent upon activity of PI3K, AKT (also known as protein kinase B), and the downstream kinase FRAP (FKBP-rapamycin-associated protein). (asm.org)
  • interaction
  • In addition, an interaction was detected by two-hybrid analysis between Gβ and Cdc24p ( 53 ), and Cdc42p-GTP was shown to bind to and activate Ste20p ( 46 ). (asm.org)
  • regulators
  • JNK (c-Jun NH 2 -terminal kinase) is thought to be among the major regulators of flow-dependent inflammatory gene expression in endothelial cells in atherosclerosis. (ahajournals.org)
  • endothelial cells
  • In this study, we investigate the role of lipid rafts and integrin α5 in regulating the inflammatory response in endothelial cells (ECs) under atheroprone versus atheroprotective flow. (pnas.org)
  • shear
  • 10-12 Our work has shown that in ECs plated on FN, but not on basement membrane or Coll, shear activates the inflammatory mediators NF-κB and p21-activated kinase (PAK), suggesting that early changes in the subendothelial matrix in atheroprone regions of the vasculature may contribute to atherogenesis through promotion of an activated EC phenotype. (ahajournals.org)
  • Membrane lipid rafts and integrins are crucial for shear stress-regulated endothelial function. (pnas.org)
  • atheroprone
  • Interestingly, oscillatory flow activates most of the same events in a sustained manner, recapitulates features of atheroprone regions of arteries in vivo, and has been used to model complex flow profiles found in vivo. (ahajournals.org)
  • gene
  • As a junior faculty member at UC San Diego, her group reported the first endothelial expression and biological function regulating endothelial junctional stability of CCM gene product protein KRIT1. (ucla.edu)
  • This analysis reveals the importance of using different cell types to gain a thorough understanding of gene function across the genome and, in the case of kinases, the difficulties of using the differential gene expression to predict function. (biomedcentral.com)
  • growth
  • However, other papers also suggested that androgens could negatively regulate the growth of mammary epithelial and breast cancer cells ( 5 - 7 ). (rupress.org)
  • Differentially regulated high-affinity iron assimilation systems support growth of the various cell types in the dimorphic pathogen Talaromyces marneffei. (nih.gov)
  • RHOA
  • VAV-2 is rapidly phosphorylated by c-Src upon stimulation by Ephrin-A [ 4 ] and activates RhoA [ 8 ]. (bio-rad.com)