The CDC25 domain comprises approximately 500 amino acids and was first identified in the CDC25 protein in budding yeast (Saccharomyces cerevisiae). (wikipedia.org)
Cdc42 and/or Rac homologs are found in fruit flies, round-worms and budding yeast. (biomedcentral.com)
Superfamily2
While different subfamilies of Ras superfamily GTPases have a conserved GTP binding domain, this is not the case for GEFs. (wikipedia.org)
GTPases are active when bound to GTP and inactive when bound to GDP, allowing their activity to be regulated by GEFs and the opposing GTPase activating proteins (GAPs). (wikipedia.org)
The binding of GEFs to their GTPase substrates catalyzes the dissociation of GDP, allowing a GTP molecule to bind in its place. (wikipedia.org)
After GDP has disassociated from the GTPase, GTP generally binds in its place, as the cytosolic ratio of GTP is much higher than GDP at 10:1. (wikipedia.org)
The binding of GTP to the GTPase results in the release of the GEF, which can then activate a new GTPase. (wikipedia.org)
Thus, GEFs both destabilize the GTPase interaction with GDP and stabilize the nucleotide-free GTPase until a GTP molecule binds to it. (wikipedia.org)
GAPs (GTPase-activating protein) act antagonistically to inactivate GTPases by increasing their intrinsic rate of GTP hydrolysis. (wikipedia.org)
GDP remains bound to the inactive GTPase until a GEF binds and stimulates its release. (wikipedia.org)
These regions and the phosphate-binding loop of the GTPase interact with the phosphates of the nucleotide and a coordinating magnesium ion to maintain high affinity binding of the nucleotide. (wikipedia.org)
GEF binding induces conformational changes in the P loop and switch regions of the GTPase while the rest of the structure is largely unchanged. (wikipedia.org)
When the GEF binds the GTPase, the phosphate groups are released first and the GEF is displaced upon binding of the entering GTP molecule. (wikipedia.org)
Though this general scheme is common among GEFs, the specific interactions between the regions of the GTPase and GEF vary among individual proteins. (wikipedia.org)
Many, but not all, of these effectors contain a conserved 18 amino-acid binding motif that has been termed CRIB (Cdc42-Rac interactive binding), PBD (p21-binding domain) or GBD (GTPase-binding domain) [ 4 ]. (biomedcentral.com)
In a screen for suppressors of SigD R468A -induced growth arrest by overexpression of a yeast cDNA library, the Cdc42 GTPase was isolated. (microbiologyresearch.org)
Mammalian2
Many of the mammalian Dbl family proteins are tissue-specific and their number in Metazoa varies in proportion of cell signaling complexity. (wikipedia.org)
In mammalian cells, as many as twenty types of protein have been reported to bind to activated Cdc42 [ 2 ]. (biomedcentral.com)
Kinases3
This motif is found in Cdc42/Rac-associated proteins such as the protein kinases Pak, MRCK and Ack, the adaptor proteins Spec and WASP, and, in degenerate form, in the kinases MLK, Mekk4, adaptor Par6, scaffold protein IRSp53, and the Borg proteins. (biomedcentral.com)
A variety of approaches, including biochemical purification, gene isolation by homology, and genetic screens, have been successfully used for the identification of putative protein kinases and phosphatases. (rupress.org)
Subfamilies1
The basic signaling properties of two major subgroups of Rho GTPases - the Cdc42 and Rac subfamilies - are highly conserved amongst all eukaryotes, but the means by which they act are not well understood. (biomedcentral.com)
Reorganization1
Requirement of Cdc42 for Salmonella typhimurium -induced cytoskeletal reorganization and nuclear responses in cultured cells. (microbiologyresearch.org)
Effector2
Although dozens of proteins act downstream of these GTPases, a comparison of effector proteins from evolutionarily diverse organisms suggests that six groups of proteins serve as the core machinery for signaling from Cdc42 and Rac. (biomedcentral.com)
Modulation of chloride secretory responses and barrier function of intestinal epithelial cells by the Salmonella effector protein SigD. (microbiologyresearch.org)
Evolutionarily1
The analysis of Cdc42 and Rac function in evolutionarily distant organisms is useful as a tool to uncover the basic activities of these proteins. (biomedcentral.com)
In addition, they play important roles in gene transcription (via activation of mitogen activated protein (MAP) kinase pathways and, in higher eukaryotes, the transcription factor NFκB), generation of reactive oxygen species, apoptosis, and cell-cycle progression. (biomedcentral.com)
Lipid1
Another distinction that has been drawn contrasts the constitutive and the regulated pathways to distinguish the ongoing transport of protein and lipid to the cell surface from the ability to secrete hormones and transmitters in response to specific stimuli. (sdbonline.org)
Mediate2
Cdc42 and Rac - ancient, highly conserved, small GTPases - mediate extracellular signals, triggering changes in transcription and in the actin cytoskeleton. (biomedcentral.com)
Protein phosphorylation can regulate enzyme function, mediate protein-protein interactions, alter subcellular localization, and control protein stability. (rupress.org)
Interact1
and proteins that interact with members of the Arp2/3 complex and hence the actin cytoskeleton (Table 1 ). (biomedcentral.com)
Pathways2
Within neurons, multiple pathways are known to transport proteins and transmitters to the cell surface. (sdbonline.org)
Two important pathways were examined in the current study: (1) a basic pathway of exocytosis that brings new proteins to the cell surface and permits the cell to grow, and (2) synaptic transmission, a specialized form of exocytosis, regulated by Ca 2+ entry, in which vesicles already present at synapses fuse with the membrane and recycle locally (Murthy, 2003). (sdbonline.org)
Function4
In an effort to understand the fundamental signaling elements, or 'core machinery', required for the function of these GTPases, we describe here the conservation and functional similarities of Cdc42 and Rac effectors in five different species: plant, yeast, fruit fly, roundworm and human. (biomedcentral.com)
This activity is strongly conserved and probably represents a primordial function of these proteins. (biomedcentral.com)
It is concluded that the Salmonella SigD protein deprived of its phosphatase activity is able to disrupt yeast morphogenesis by interfering with Cdc42 function, opening the possibility that the SigD N-terminal region might directly modulate small GTPases from the host during infection. (microbiologyresearch.org)
Nuclear1
For example, the Ran GEF, RCC1, is present in the nucleus while the Ran GAP is present in the cytosol, modulating nuclear import and export of proteins. (wikipedia.org)
Organisms1
The reversible phosphorylation of proteins on serine, threonine, and tyrosine residues represents a fundamental strategy used by eukaryotic organisms to regulate a host of biological functions, including DNA replication, cell cycle progression, energy metabolism, and cell growth and differentiation. (rupress.org)
The CDC25 homology domain, also called the RasGEF domain, is the catalytic domain of many Ras GEFs, which activate Ras GTPases. (wikipedia.org)
Dbl-like RhoGEFs are characterized by the presence of a Dbl Homology domain (DH domain), responsible for GEF catalytic activity for Rho GTPases. (wikipedia.org)
Common1
In this article, we focus on the signaling mechanisms of two of these three subgroups, Cdc42 and Rac, as they are often linked in their physiological functions and have several effectors in common. (biomedcentral.com)
Share1
The functional domains of these GEF families are not structurally related and do not share sequence homology. (wikipedia.org)
Activity1
In vitro GAP activity towards RhoA, Rac1 and Cdc42 is not a prerequisite for YopE induced HeLa cell cytotoxicity. (microbiologyresearch.org)
Origin1
This broad distribution across widely divergent eukaryotic species suggests that Cdc42 and Rac GTPases have an ancient origin, perhaps even predating that of their cousin Ras. (biomedcentral.com)
Regions1
Such processes require membrane traffic to particular domains of the cell surface, in order to insert proteins at restricted regions of the membrane, to enlarge particular regions of the cell membrane, or to signal asymmetrically to neighboring cells. (sdbonline.org)
Alter1
However, there are some similarities in how different GEFs alter the conformation of the G protein nucleotide-binding site. (wikipedia.org)
Traffic4
By regulating filamentous actin, Cdc42 and Rac exert a profound effect on cell shape, polarity, migration, cell:cell and cell:matrix adhesion, protein traffic, and cytokinesis. (biomedcentral.com)
The exocyst complex, a set of eight proteins first identified from secretory mutants in yeast, is an attractive candidate for mediating directed traffic. (sdbonline.org)
Neurons generate their polarity by directing membrane traffic to growing neurites and growth cones, and by sorting proteins differentially between the axon and dendrites. (sdbonline.org)
This protein is required for many aspects of membrane traffic within neurons, including the elaboration of neurites, but the release of neurotransmitter at the synapse is independent of this exocyst component (Murthy, 2003). (sdbonline.org)
Activation1
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains involved in the activation of small GTPases. (wikipedia.org)