SEARCH · PubMed Health

Results for “cdc42 GTP-Binding Protein”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1995

Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases.

Ral proteins constitute a distinct family of Ras-related GTPases. Although similar to Ras in amino acid sequence, Ral proteins are activated by a unique nucleotide exchange factor and inactivated by a distinct GTPase-activating protein. Unlike Ras, they fail to promote transformed foci when activated versions are expressed in cells. To identify downstream targets that might mediate a Ral-specific function, we used a Saccharomyces cerevisiae-based interaction assay to clone a novel cDNA that encodes a Ral-binding protein (RalBP1). RalBP1 binds specifically to the active GTP-bound form of RalA and not to a mutant Ral with a point mutation in its putative effector domain. In addition to a Ral-binding domain, RalBP1 also contains a Rho-GTPase-activating protein domain that interacts preferentially with Rho family member CDC42. Since CDC42 has been implicated in bud site selection in S. cerevisiae and filopodium formation in mammalian cells, Ral may function to modulate the actin cytoskeleton through its interactions with RalBP1.

Amino Acid Sequence↗

PubMed1994

Activation of phosphoinositide 3-kinase activity by Cdc42Hs binding to p85.

The Ras-like GTPase Cdc42 is essential for cell polarity and bud site assembly in Saccharomyces cerevisiae by regulating cell cycle-dependent reorganization of cortical cytoskeletal elements. However, its role in mammalian cells is unknown. To identify potential effectors of Cdc42Hs, we incubated lysates from NIH 3T3 fibroblasts or PC12 cells with immobilized glutathione S-transferase (GST)-Cdc42Hs fusion proteins bound to different guanine nucleotides and observed a specific association between the 85-kDa subunit (p85) of phosphatidylinositol 3-kinase (PI 3-kinase) and GTP gamma S (guanosine 5'-3-O-(thio)triphosphate)-bound GST-Cdc42Hs. Recombinant p85 formed a complex with GTP gamma S-bound GST-Cdc42Hs and with a GTPase-defective GTP-bound GST-Cdc42Hs-Q61L mutant, but not with a GTP gamma S-bound, effector domain GST-Cdc42HsT35A mutant. Both the Rho-GAP homology domain of p85 and the Cdc42Hs-GAP competitively inhibited the binding of recombinant p85 to Cdc42Hs. In addition, PI 3-kinase activity immunoprecipitated from cell lysates with anti-p85 antibody was stimulated 2-4-fold by GST-Cdc42-GTP gamma S. Similar interactions were observed between p85 and GST-Rac1-GTP gamma S but not between p85 and GST-RhoA-GTP gamma S. These findings suggest that PI 3-kinase, through the Rho-GAP homology domain of p85, can couple to the effector domain of Cdc42Hs and that p85 may be a target for the GTP-bound forms of Cdc42Hs and Rac1.

3T3 Cells↗

PubMed1990

Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity.

The Saccharomyces cerevisiae CDC42 gene product is involved in the morphogenetic events of the cell division cycle; temperature-sensitive cdc42 mutants are unable to form buds and display delocalized cell-surface deposition at the restrictive temperature (Adams, A. E. M., D. I. Johnson, R. M. Longnecker, B. F. Sloat, and J. R. Pringle. 1990. J. Cell Biol. 111:131-142). To begin a molecular analysis of CDC42 function, we have isolated the CDC42 gene from a yeast genomic DNA library. The use of the cloned DNA to create a deletion of CDC42 confirmed that the gene is essential. Overexpression of CDC42 under control of the GAL10 promoter was not grossly deleterious to cell growth but did perturb the normal pattern of selection of budding sites. Determination of the DNA and predicted amino acid sequences of CDC42 revealed a high degree of similarity in amino acid sequence to the ras and rho (Madaule, P., R. Axel, and A. M. Myers. 1987. Proc. Natl. Acad. Sci. 84:779-783) families of gene products. The similarities to ras proteins (approximately 40% identical or related amino acids overall) were most pronounced in the regions that have been implicated in GTP binding and hydrolysis and in the COOH-terminal modifications leading to membrane association, suggesting that CDC42 function also involves these biochemical properties. The similarities to the rho proteins (approximately 60% identical or related amino acids overall) were more widely distributed through the coding region, suggesting more extensive similarities in as yet undefined biochemical properties and functions.

Amino Acid Sequence↗

PubMed1992

A homologue of the ras-related CDC42 gene from Schizosaccharomyces pombe.

A cDNA was isolated from the fission yeast, Schizosaccharomyces pombe, using mixed oligodeoxyribonucleotides encoding part of the GTP-binding site of the ras superfamily. The encoded protein is the homologue of the budding yeast CDC42 gene product and the human proteins, CDC42Hs and G25K.

Amino Acid Sequence↗

PubMed1991

Mutational analysis of CDC42Sc, a Saccharomyces cerevisiae gene that encodes a putative GTP-binding protein involved in the control of cell polarity.

The Saccharomyces cerevisiae CDC42 gene product, a member of the ras superfamily of low-molecular-weight GTP-binding proteins, is involved in the control of cell polarity. We have analyzed the effects of three CDC42 mutations (Gly to Val-12, Gln to Leu-61, and Asp to Ala-118) in the putative GTP-binding and hydrolysis domains and one mutation (Cys to Ser-188) in the putative isoprenylation site. The first three mutations resulted in either a dominant-lethal or dose-dependent dominant-lethal phenotype when present on plasmids in haploid cdc42-1ts or wild-type strains. Both wild-type and cdc42-1ts cells carrying plasmids (pGAL) with either the CDC42Val-12 or CDC42Leu-61 alleles under the control of a GAL promoter were arrested with a novel phenotype of large cells with elongated or multiple buds. Cells carrying pGAL-CDC42Ala-118 were arrested as large, round, unbudded cells reminiscent of cdc42-1ts arrested cells. The different phenotype of the CDC42Ala-118 mutant versus the CDC42Val-12 and CDC42Leu-61 mutants was unexpected since the phenotypes of all three analogous ras mutants were similar to each other. This suggests that aspects of the biochemical properties of the Cdc42 protein differ from those of the Ras protein. The cdc42Ser-188 mutant gene was incapable of complementing the cdc42-1ts mutation and was recessive to both wild-type and cdc42-1ts. In double-mutant alleles, the cdc42Ser-188 mutation was capable of suppressing the dominant lethality associated with the three putative GTP-binding and hydrolysis mutations, suggesting that isoprenylation is necessary for the activity of the wild-type and mutant proteins.

Amino Acid Sequence↗

PubMed1994

A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways.

Transfection of NIH3T3 cells with an osteosarcoma expression cDNA library led to the appearance of foci of morphologically transformed cells which were found to harbor a novel oncogene, ost. The ost product was activated by truncation of the N-terminal domain of the ost proto-oncogene and was highly tumorigenic in nude mouse assays. The proto-ost cDNA, isolated subsequently, encodes a predicted protein of 100 kDa containing DH (Db1 homology) and PH (pleckstrin homology) domains. Ost is mainly phosphorylated on serine and localized in the cytoplasm. Purified Ost protein catalyzed guanine nucleotide exchange on RhoA and Cdc42 among the Rho and Ras family members tested, indicating that Ost can activate these small GTP-binding proteins. Ost did not detectably associate with RhoA or Cdc42, but interacted specifically with the GTP-bound form of Rac1, suggesting that Ost can function as an effector of Rac1. These results suggest that Ost is a critical regulatory component which links pathways that signal through Rac1, RhoA and Cdc42. Of the tissues examined, expression of ost was the highest in brain and could be localized to neurons and alpha-tanycytes, suggesting that Ost may participate in axonal transport in these specialized cells.

3T3 Cells↗

PubMed1989

Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1.

Genes CDC24, CDC42, and CDC43 are required for the establishment of cell polarity and the localization of secretion in Saccharomyces cerevisiae; mutants defective in these genes fail to form buds and display isotropic expansion of the cell surface. To identify other genes that may be involved in these processes, we screened yeast genomic DNA libraries for heterologous genes that, when overexpressed from a plasmid, can suppress a temperature-sensitive cdc24 mutation. We identified four such genes. One of these proved to be CDC42, which has previously been shown to be a member of the rho (ras-homologous) family of genes, and a second is a newly identified ras-related gene that we named RSR1. RSR1 maps between CDC62 and ADE3 on the right arm of chromosome VII; its predicted product is approximately 50% identical to other proteins in the ras family. Deletion of RSR1 is nonlethal but disrupts the normal pattern of bud site selection. Although both CDC42 and RSR1 can suppress cdc24 and both appear to encode GTP-binding proteins, these genes do not themselves appear to be functionally interchangeable. However, one of the other genes that was isolated by virtue of its ability to suppress cdc24 can also suppress cdc42. This gene, named MSB1, maps between ADE9 and HIS3 on the right arm of chromosome XV.

Amino Acid Sequence↗

PubMed1994

Molecular cloning and characterization of yeast rho GDP dissociation inhibitor.

We have previously isolated rho GDP dissociation inhibitor (rho DGI) from bovine brain and characterized it. Bovine rho GDI is a protein of a M(r) of 23,421 with 204 amino acids. rho GDI inhibits the GDP/GTP exchange reaction of post-translationally lipid-modified small GTP-binding proteins (G proteins) of the rho family, including the rho, rac, and cdc42 subfamilies, and keeps them in the GDP-bound inactive form. In the present study, we first purified rho GDI from the cytosol fraction of the yeast Saccharomyces cerevisiae and isolated its gene. Yeast rho GDI gene had an open reading frame without introns encoding a protein of a M(r) of 23,138 with 202 amino acids. Yeast rho GDI protein was 36% identical with bovine rho GDI. Yeast rho GDI expressed in Escherichia coli was active not only on yeast rho1 but also on mammalian rho family members which were post-translationally modified. Disruption of rho GDI did not induce apparent phenotypes, whereas overexpression of yeast or bovine rho GDI resulted in the inhibition of cell growth. These results indicate that rho GDI exists and regulates the function of the rho family members in yeast.

Amino Acid Sequence↗

PubMed1995

Rho-ADP-ribosylating exoenzyme from Bacillus cereus. Purification, characterization, and identification of the NAD-binding site.

The ADP-ribosyltransferase produced by a pathogenic strain of Bacillus cereus was purified to near homogeneity. The transferase is a 28,000 Da molecular mass enzyme with a pI of 10.3. The specific enzyme activity is 7.0 nmol of ADP-ribose min-1 mg-1 with a Km for NAD of 0.3 microM. Partial amino acid sequence analysis of the exoenzyme reveals no significant homology to Clostridium botulinum C3 nor to Clostridium limosum exoenzyme. The novel exoenzyme selectively modifies the small GTP-binding proteins of the Rho family presumably at the same acceptor amino acid (Asn-41) as determined for C3. Besides cellular Rho, recombinant RhoA and -B are substrates for the exoenzyme. However, recombinant Rac1 and CDC42, although belonging to the Rho family, are not modified. B. cereus exoenzyme was photolabeled with [carbonyl-14C]NAD resulting in inhibition of ADP-ribosyltransferase and NAD-glycohydrolase activity. A glutamic acid residue was identified as part of the NAD-binding site which corresponds to Glu-174 of C3. This glutamic acid is located in a domain which shows high homology with the C-terminal part of C3 exoenzyme, C. limosum exoenzyme, and Staphylococcus aureus EDIN and which probably represents the catalytic site of the transferases. The data indicate that B. cereus exoenzyme is a novel member of the family of C3-like ADP-ribosyltransferases which share the same substrate protein Rho and which have an identical highly conserved catalytic domain.

ADP Ribose Transferases↗

PubMed1995

Rho-related proteins: actin cytoskeleton and cell cycle.

The past year has produced an abundance of data on the function and regulation of Rho-related GTP-binding proteins. In mammalian cells, it has been shown that Rho is required for contractile ring assembly at cell division, as well as for regulating extracellular factor induced actin reorganization. In addition, many new regulators and/or potential targets for Rho, Rac and Cdc42 have been characterized, including several oncogene products, protein kinases and signal transducing proteins in mammalian cells, and genes defined by cell cycle or bud emergence mutations in yeast. These provide further connections between Rho-related proteins, signal transduction pathways and changes in actin organization during cell cycle entry and progression.

Actins↗

PubMed1991

Yeast BUD5, encoding a putative GDP-GTP exchange factor, is necessary for bud site selection and interacts with bud formation gene BEM1.

Cells of the yeast S. cerevisiae choose bud sites in an axial or bipolar spatial pattern depending on their cell type. We have identified a gene, BUD5, that resembles BUD1 and BUD2 in being required for both patterns; bud5- mutants also exhibit random budding in all cell types. The BUD5 nucleotide sequence predicts a protein of 538 amino acids that has similarity to the S. cerevisiae CDC25 product, an activator of RAS proteins that catalyzes GDP-GTP exchange. Two potential targets of BUD5 are known: BUD1 (RSR1) and CDC42, proteins involved in bud site selection and bud formation, respectively, that have extensive similarity to RAS. We also show that BUD5 interacts functionally with a gene, BEM1, that is required for bud formation. This interaction provides further support for the view that products involved in bud site selection guide the positioning of a complex necessary for bud formation.

Amino Acid Sequence↗

PubMed1994

Activation of rat liver phospholipase D by the small GTP-binding protein RhoA.

Stimulation of phospholipase D by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) in rat liver plasma membranes indicates the involvement of GTP-binding proteins. We used RhoGDI, an inhibitor of GDP dissociation from small GTP-binding proteins of the Rho family, to determine the involvement of these proteins. Incubation, and subsequent washing, of plasma membranes with RhoGDI dose-dependently diminished GTP gamma S-stimulated phospholipase D activity, as determined by accumulation of phosphatidylethanol in the presence of ethanol. Incubation with RhoGDI also caused a rapid and dose-dependent appearance of RhoA in the wash, which was associated with the inhibition of phospholipase D. RhoGDI also rapidly extracted Cdc42 from membranes, but Rac1 was not extracted. Full reconstitution of GTP gamma S-stimulated phospholipase D in RhoGDI-washed membranes was achieved with recombinant RhoA. There was partial reconstitution with Rac1 and no enhancement with Cdc42 or ADP-ribosylation factor. The response to RhoA was dose-dependent (EC50 = 0.5 microM). ADP-ribosylation of RhoA by Clostridium botulinum C3 exoenzyme did not affect its ability to recover GTP gamma S-stimulated phospholipase D activity in RhoGDI-washed membranes. These findings support a role for GTP-binding proteins of the Rho family in the activation of membrane-associated phospholipase D and implicate RhoA as the major protein involved.

Adenosine Diphosphate Ribose↗

PubMed1994

Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion.

The small GTPases of the Rac/Rho/Cdc42 subfamily are implicated in actin cytoskeleton-membrane interaction in mammalian cells and budding yeast. The in vivo functions of these GTPases in multicellular organisms are not known. We have cloned Drosophila homologs of rac and CDC42, Drac1, and Dcdc42. They share 70% amino acid sequence identity with each other, and both are highly expressed in the nervous system and mesoderm during neuronal and muscle differentiation, respectively. We expressed putative constitutively active and dominant-negative Drac1 proteins in these tissues. When expressed in neurons, Drac1 mutant proteins cause axon outgrowth defects in peripheral neurons without affecting dendrites. When expressed in muscle precursors, they cause complete failure of, or abnormality in, myoblast fusion. Expressions of analogous mutant Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis.

Actins↗

PubMed1995

Resolved phospholipase D activity is modulated by cytosolic factors other than Arf.

Phospholipase D, which has been extracted from porcine brain membranes and chromatographically enriched 100-fold, was activated better by impure preparations of Arf than by purified or recombinant Arf. Examination of brain cytosol with this enriched preparation of PLD activity revealed at least three stimulatory components. One of these is Arf or the first cytoplasmic factor. A second peak of PLD-stimulating activity (cytoplasmic factor II, CFII) was resolved from Arf by anion exchange and gel filtration. This CFII can be further separated into multiple activities by chromatography with heparin-agarose. The activities were differentiated by their stimulatory properties as measured in the absence or presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) alone and in the presence of added Arf and GTP gamma S. While all of the CFII pools stimulated PLD activity to some degree and showed synergistic activation when administered in conjunction with Arf, they could be classified into two groups with distinct behavior. When used together, pools from the two respective groups showed synergistic activation of PLD. The first set of pools contained the RhoA monomeric G protein. Recombinant RhoA was used to show that it could indeed activate this enriched PLD activity and act synergistically with Arf proteins. A related monomeric G protein, Cdc42, was also effective. The second set of CFII pools were devoid of RhoA and, in contrast to the first group, demonstrated significant stimulating activity in the absence of guanine nucleotides. These data indicate that the PLD activity from brain can be modulated by several cytosolic factors and that Arf-sensitive PLD may represent a complex activity that can be regulated in an interactive fashion by a variety of cellular signaling events.

ADP-Ribosylation Factors↗

PubMed1992

The small GTP-binding proteins in the cytosol of insulin-secreting cells are complexed to GDP dissociation inhibitor proteins.

Ras-related small GTP-binding proteins (SMGs) exist in a cytosolic and a membrane-bound pool. The mechanism regulating the intracellular distribution of SMGs remains to be elucidated. We have, therefore, investigated the properties of SMGs expressed in cells of the insulin-secreting lines RINm5F and HIT-T15. Phase-partitioning analysis revealed that smg25A/rab3A as well as all the SMGs in the 23-27 kDa range, labeled by radioactive GTP after blotting, were hydrophobic, regardless of their subcellular distribution. In contrast, the cytosolic forms of ADP ribosylation factor, rho, and CDC42 were hydrophilic. The cytosolic pool of the 23-27-kDa group, including smg25A/rab3A, sedimented in a sucrose density gradient as complexes with an apparent M(r) of about 80,000, whereas rho and CDC42 were recovered in 45-kDa complexes. ARF, however, was uncomplexed (M(r) close to 20,000). The 80-kDa aggregates were likely to be formed by 1:1 complexes with the regulatory protein smg25/GDP dissociation inhibitor (smg25/GDI). In fact, pure smg25/GDI by sucrose gradient exhibited a molecular mass of 55 kDa, but cosedimented with the 80-kDa complexes in cytosolic extracts of insulin-secreting cells. Moreover, purified smg25/GDI was able to extract the SMGs of the 23-27-kDa group from the membranes. Similarly, in cytosolic extracts, rho/GDI cosedimented with the 45-kDa aggregates. Blocking the synthesis of isoprenoid groups with lovastatin resulted in the appearance in the cytosol of SMGs that were hydrophilic. These SMGs were found to sediment with an apparent M(r) close to 25,000 and to be unable to form complexes with smg25/GDI. Lovastatin treatment also caused the accumulation of the noncomplexed form of CDC42 but not of rho proteins. We propose that 1) except for ARF, all the SMGs detected in the cytosol of insulin-secreting cells are associated in 1:1 complexes with their regulatory proteins; 2) the different SMGs can be subdivided into functional groups according to the regulatory protein bound to them; 3) the formation of the 80-kDa complexes with smg25/GDI and of the CDC42 complexes with rho/GDI necessitate the correct carboxyl-terminal post-translational modification of the SMGs.

Animals↗

PubMed1995

A role for Rac in Tiam1-induced membrane ruffling and invasion.

Rho-like GTPases have been implicated in the regulation of the actin cytoskeleton which controls the morphology, adhesion and motility of cells. Like Ras proteins, they become activated when bound GDP is exchanged for GTP, a process catalysed by GDP-dissociation stimulator (GDS) proteins. Several GDS proteins specific for Rho-like GTPases have been identified. Most of these contain a conserved catalytic domain, the DBL-homology (DH) domain, and activate Cdc42 or Rho but not Rac. We have isolated the invasion-inducing Tiam1 gene, which also encodes a protein with a DH domain. Here we show that Tiam1 is a GDS protein for Rho-like GTPases in vitro. In fibroblasts, Tiam1 induces a similar phenotype as constitutively activated (V12)Rac1, including membrane ruffling, and this is inhibited by dominant negative (N17)Rac1. Moreover, T-lymphoma cells expressing V12Rac1 become invasive, indicating that the Tiam1-Rac signalling pathway could be operating in the invasion and metastasis of tumour cells.

3T3 Cells↗

PubMed1995

CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing disc epithelium.

Cdc42 and Rac1 are members of the rho family of small guanosinetriphosphatases and are required for a diverse set of cytoskeleton-membrane interactions in different cell types. Here we show that these two proteins contribute differently to the organization of epithelial cells in the Drosophila wing imaginal disc. Drac1 is required to assemble actin at adherens junctions. Failure of adherens junction actin assembly in Drac1 dominant-negative mutants is associated with increased cell death. Dcdc42, on the other hand, is required for processes that involve polarized cell shape changes during both pupal and larval development. In the third larval instar, Dcdc42 is required for apico-basal epithelial elongation. Whereas normal wing disc epithelial cells increase in height more than twofold during the third instar, cells that express a dominant-negative version of Dcdc42 remain short and are abnormally shaped. Dcdc42 localizes to both apical and basal regions of the cell during these events, and mediates elongation, at least in part, by effecting a reorganization of the basal actin cytoskeleton. These observations suggest that a common cdc42-based mechanism may govern polarized cell shape changes in a wide variety of cell types.

Actins↗

PubMed1992

Ras-related GTPases and the cytoskeleton.

Incorporation of the available data on rac in neutrophils, CDC42 in yeast, and rho in fibroblasts suggests a general model for the function of rho-like GTPase (Figure 1). Conversion of an inactive cytoplasmic rho-related p21GDP/GDI complex to active p21. GTP occurs by inhibition of GAP and/or stimulation of exchange factors in response to cell signals. p21.GTP is then able to interact with its target at the plasma membrane. This could result in a conformational change in the target, enabling it to bind cytosolic protein(s). Alternatively, p21.GTP could be actively involved in transporting cytosolic protein(s) to the target. A GAP protein, perhaps intrinsic to the complex, would stimulate GTP hydrolysis allowing p21.GDP to dissociate. Solubilization of p21GDP by interaction with GDI would complete a cycle. What about the nature of the final complex? The rac-regulated NADPH oxidase complex in neutrophils is currently the best understood and most amenable to further biochemical analysis. Two plasma-membrane bound subunits encode the catalytic function necessary for producing superoxide, but the two cytosolic proteins, p47 and p67, are essential for activity. Why the complexity? Production of superoxide is tightly coordinated with phagocytosis, a membrane process driven by rearrangement of cortical actin. This is not unrelated to the membrane ruffling and macropinocytosis that we observe in fibroblasts microinjected with p21rac. It is tempting to speculate, therefore, that in neutrophils rac is involved not only in promoting the assembly of the NADPH oxidase but also in the coordinate reorganization of cortical actin leading to phagocytosis. For CDC42 controlled bud assembly in yeast, the components of the plasma-membrane complex are not so clear. By analogy with rac in neutrophils, it seems likely that CDC42 is involved in promoting the assembly of cytosolic components at the bud site on the plasma membrane. These putative cytosolic proteins have not yet been identified, but BEM1 and ABP1 are two possible candidates. The biochemical basis for the stimulation of adhesion plaques and actin stress fibers by p21rho in fibroblasts is also unclear. However, components of the adhesion plaque such as vinculin and talin are known to be cytosolic when not complexed with integrin receptors, and rho could be involved in regulating their assembly into the adhesion plaque. Several things are still difficult to incorporate into this model. First the target for CDC42, the bud site, although not yet structurally defined requires the activity of another small GTPase, BUD1. Similarly, in activated neutrophils, the NADPH oxidase is found in a complex with rap1, the mammalian homologue of BUD1 (BoKoch et al., 1989). It seems likely, therefore, that the target is not simply a plasma-membrane protein but may be a complex of proteins whose formation is under the control of the rap1/BUD1 GTPase. The other black box in this model is the actin connection: activation of bud assembly by CDC42 is followed by actin polymerization, activation of NADPH oxidase in neutrophils occurs concomitantly with phagocytosis, a cortical actin-dependent process, and p21rho in fibroblasts couples the formation of adhesion plaques to actin stress fibers. One possible link between the GTPase-driven assembly of a plasma-membrane complex and actin polymerization could involve the SH3 domain. Interestingly, both p47 and p67 and yeast ABP1 and BEM1 have SH3 domain. If rho-like GTPases recognize plasma-membrane targets already associated with cortical actin, then this could promote an interaction with a subset of SH3-containing proteins. The result of this would be a GTPase-regulated aggregation of a group of proteins at a single site in the plasma membrane. It is not too difficult to imagine biological processes where such a spatial integration of different biochemical activities would be essential: coupling the assembly of bud components to the formation of actin fibers in yeast; or the activation of NADPH oxidase to phagocytosis in neutrophils; or the assembly of adhesion plaques and the formation of actin stress fibers in fibroblasts are just three examples that have emerged so far. In conclusion, although rho-like GTPases clearly have distinct roles in different mammalian cell types and in yeast, their underlying mechanism of action appears to be strikingly similar. Whether this will remain so when there are some biochemical data to back up these initial observations, time will tell.

Actins↗