Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ZAK negatively regulates RhoGDIbeta-induced Rac1-mediated hypertrophic growth and cell migration.

ABSTRACT: RhoGDIbeta, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIbeta plays a previously undefined role in regulating Rac1 expression through transcription to induce hypertrophic growth and cell migration and that these functions are blocked by the expression of a dominant-negative form of Rac1. We also demonstrated that knockdown of RhoGDIbeta expression by RNA interference blocked RhoGDIbeta-induced Rac1 expression and cell migration. We demonstrated that the co-expression of ZAK and RhoGDIbeta in cells resulted in an inhibition in the activity of ZAK to induce ANF expression. Knockdown of ZAK expression in ZAK-RhoGDIbeta-expressing cells by ZAK-specific RNA interference restored the activities of RhoGDIbeta.

SUBMITTER: Huang CY

PROVIDER: S-EPMC2703632 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

ZAK negatively regulates RhoGDIbeta-induced Rac1-mediated hypertrophic growth and cell migration.

Huang Chih-Yang CY Yang Li-Chiu LC Liu Kuan-Yu KY Chang I-Chang IC Liao Pao-Hsin PH Chou Janet Ing-Yuh JI Chou Ming-Yung MY Lin Wei-Wen WW Yang Jaw-Ji JJ

Journal of biomedical science 20090618

RhoGDIbeta, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIbeta plays a previously undefined role in regulating Rac1 expression through transcription to induce hypertrophic growth and cell migration and that these functions are blocked by the expression of a dominant-negative form of Rac1. We also demonstrated that knockdown of RhoGDIbeta expression by RNA interference blocked RhoGDIbeta-in ...[more]

PMID: 19538723

Similar Datasets

RhoGDIbeta-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK.

Project description:We found that overexpression of RhoGDIbeta, a Rho GDP dissociation inhibitor, induced hypertrophic growth and suppressed cell cycle progression in a cultured cardiomyoblast cell line. Knockdown of RhoGDIbeta expression by RNA interference blocked hypertrophic growth. We further demonstrated that RhoGDIbeta physically interacts with ZAK and is phosphorylated by ZAK in vitro, and this phosphorylation negatively regulates RhoGDIbeta functions. Moreover, the ZAK-RhoGDIbeta interaction may maintain ZAK in an inactive hypophosphorylated form. These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction. Knockdown of ZAK expression in ZAK- and RhoGDIbeta-expressing cells by ZAK-specific RNA interference restored the full functions of RhoGDIbeta.

| S-EPMC2653512 | biostudies-literature

N?-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway.

Project description:Background:Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. N?-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown. Methods and Results:In this study, we used anterior tibiofibular vascular samples from diabetic foot amputation patients and accident amputation patients, and histological and cytological tests were performed using a diabetic ApoE-/- mouse model and primary peritoneal macrophages, respectively. The results showed that the atherosclerotic plaques of diabetic foot amputation patients and diabetic ApoE-/- mice were larger than those of the control group. Inhibition of the Vav1/Rac1 pathway reduced vascular plaques and promoted the migration of macrophages to lymph nodes. Transwell and wound healing assays showed that the migratory ability of macrophage-derived foam cells was inhibited by CML. Cytoskeletal staining showed that advanced glycation end products inhibited the formation of lamellipodia in foam cells, and inhibition of the Vav1/Rac1 pathway restored the formation of lamellipodia. Conclusion:CML inhibits the migration of foam cells from blood vessels via the Vav1/Rac1 pathway, and this process affects the formation of lamellipodia.

| S-EPMC7064830 | biostudies-literature

PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration.

Project description:The LIM domain-containing TRIP6 (Thyroid Hormone Receptor-interacting Protein 6) is a focal adhesion molecule known to regulate lysophosphatidic acid (LPA)-induced cell migration through interaction with the LPA2 receptor. LPA stimulation targets TRIP6 to the focal adhesion complexes and promotes c-Src-dependent phosphorylation of TRIP6 at Tyr-55, which creates a docking site for the Crk Src homology 2 domain, thereby promoting LPA-induced morphological changes and cell migration. Here we further demonstrate that a switch from c-Src-mediated phosphorylation to PTPL1/Fas-associated phosphatase-1-dependent dephosphorylation serves as an inhibitory feedback control mechanism of TRIP6 function in LPA-induced cell migration. PTPL1 dephosphorylates phosphotyrosine 55 of TRIP6 in vitro and inhibits LPA-induced tyrosine phosphorylation of TRIP6 in cells. This negative regulation requires a direct protein-protein interaction between these two molecules and the phosphatase activity of PTPL1. In contrast to c-Src, PTPL1 prevents TRIP6 turnover at the sites of adhesions. As a result, LPA-induced association of TRIP6 with Crk and the function of TRIP6 to promote LPA-induced morphological changes and cell migration are inhibited by PTPL1. Together, these results reveal a novel mechanism by which PTPL1 phosphatase plays a counteracting role in regulating TRIP6 function in LPA-induced cell migration.

| S-EPMC3923842 | biostudies-literature

Cereblon regulates NK cell cytotoxicity and migration via Rac1 activation.

Project description:Rearrangement of the actin cytoskeleton is critical for cytotoxic and immunoregulatory functions as well as migration of natural killer (NK) cells. However, dynamic reorganization of actin is a complex process, which remains largely unknown. Here, we investigated the role of the protein Cereblon (CRBN), an E3 ubiquitin ligase complex co-receptor and the primary target of the immunomodulatory drugs, in NK cells. We observed that CRBN partially colocalizes with F-actin in chemokine-treated NK cells and is recruited to the immunological synapse, thus suggesting a role for this protein in cytoskeleton reorganization. Accordingly, silencing of CRBN in NK cells results in a reduced cytotoxicity that correlates with a defect in conjugate and lytic synapse formation. Moreover, CRBN depletion significantly impairs the ability of NK cells to migrate and reduces the enhancing effect of lenalidomide on NK cell migration. Finally, we provided evidence that CRBN is required for activation of the small GTPase Rac1, a critical mediator of cytoskeleton dynamics. Indeed, in CRBN-depleted NK cells, chemokine-mediated or target cell-mediated Rac1 activation is significantly reduced. Altogether our data identify a critical role for CRBN in regulating NK cell functions and suggest that this protein may mediate the stimulatory effect of lenalidomide on NK cells.

| S-EPMC9291148 | biostudies-literature

Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration.

Project description:Osteosarcoma, the most common primary bone tumor, occurs most frequently in children and adolescents and has a 5-year survival rate, which is unsatisfactory. As epidermal growth factor receptor (EGFR) positively correlates with TNM (tumor-node-metastasis) stage in osteosarcoma, EGFR may play an important role in its progression. The purpose of this study was to explore potential mechanisms underlying this correlation. We found that EGF promotes MG63 cell migration and invasion as well as stress fiber formation via Rho A activation and that these effects can be reversed by inhibiting Rho A expression. In addition, molecules downstream of Rho A, including ROCK1, LIMK2, and Cofilin, are activated by EGF in MG63 cells, leading to actin stress fiber formation and cell migration. Moreover, inhibition of ROCK1, LIMK2, or Cofilin in MG63 cells using known inhibitors or short hairpin RNA (shRNA) prevents actin stress fiber formation and cell migration. Thus, we conclude that Rho A/ROCK1/LIMK2/Cofilin signaling mediates actin microfilament formation in MG63 cells upon EGFR activation. This novel pathway provides a promising target for preventing osteosarcoma progression and for treating this cancer.

| S-EPMC5983621 | biostudies-literature

Adenosine Receptor A2B Negatively Regulates Cell Migration in Ovarian Carcinoma Cells.

Project description:The purinergic system is fundamental in the tumor microenvironment, since it regulates tumor cell interactions with the immune system, as well as growth and differentiation in autocrine-paracrine responses. Here, we investigated the role of the adenosine A2B receptor (A2BR) in ovarian carcinoma-derived cells' (OCDC) properties. From public databases, we documented that high A2BR expression is associated with a better prognostic outcome in ovarian cancer patients. In vitro experiments were performed on SKOV-3 cell line to understand how A2BR regulates the carcinoma cell phenotype associated with cell migration. RT-PCR and Western blotting revealed that the ADORA2B transcript (coding for A2BR) and A2BR were expressed in SKOV-3 cells. Stimulation with BAY-606583, an A2BR agonist, induced ERK1/2 phosphorylation, which was abolished by the antagonist PSB-603. Pharmacological activation of A2BR reduced cell migration and actin stress fibers; in agreement, A2BR knockdown increased migration and enhanced actin stress fiber expression. Furthermore, the expression of E-cadherin, an epithelial marker, increased in BAY-606583-treated cells. Finally, cDNA microarrays revealed the pathways mediating the effects of A2BR activation on SKOV-3 cells. Our results showed that A2BR contributed to maintaining an epithelial-like phenotype in OCDC and highlighted this purinergic receptor as a potential biomarker.

| S-EPMC9100769 | biostudies-literature

MYADM regulates Rac1 targeting to ordered membranes required for cell spreading and migration.

Project description:Membrane organization into condensed domains or rafts provides molecular platforms for selective recruitment of proteins. Cell migration is a general process that requires spatiotemporal targeting of Rac1 to membrane rafts. The protein machinery responsible for making rafts competent to recruit Rac1 remains elusive. Some members of the MAL family of proteins are involved in specialized processes dependent on this type of membrane. Because condensed membrane domains are a general feature of the plasma membrane of all mammalian cells, we hypothesized that MAL family members with ubiquitous expression and plasma membrane distribution could be involved in the organization of membranes for cell migration. We show that myeloid-associated differentiation marker (MYADM), a protein with unique features within the MAL family, colocalizes with Rac1 in membrane protrusions at the cell surface and distributes in condensed membranes. MYADM knockdown (KD) cells had altered membrane condensation and showed deficient incorporation of Rac1 to membrane raft fractions and, similar to Rac1 KD cells, exhibited reduced cell spreading and migration. Results of rescue-of-function experiments by expression of MYADM or active Rac1L61 in cells knocked down for Rac1 or MYADM, respectively, are consistent with the idea that MYADM and Rac1 act on parallel pathways that lead to similar functional outcomes.

| S-EPMC3078064 | biostudies-literature

Phosphorylation of EBP50 negatively regulates ?-PIX-dependent Rac1 activity in anoikis.

Project description:We demonstrated a protein kinase C (PKC)-dependent phosphorylation of canine ezrin/radixin/moesin (ERM)-binding phosphoprotein 50 (EBP50) at serine 347/348 by site-directed mutagenesis and a phospho-specific antibody. Cell fractionation and confocal imaging revealed the relocation of EBP50 from the plasma membrane to cytosol that accompanied this phosphorylation event. Increased phosphorylation at these serine residues led to the dissociation of EBP50 from ezrin and ?-PIX, which are two upstream regulators of Rac1 activation. Cells overexpressing an EBP50 mutant, mimicking serine 347/348 phosphorylation, became refractory to hepatocyte growth factor-induced cell spreading and scattering, which is normally mediated by Rac1 activation. Detachment of cells from the substratum also elicited an increase in EBP50 phosphorylation, apparently due to counteracting activities of PKC and protein phosphastase 2A, which resulted in decreased Rac1 activation and induction of anoikis. Cells overexpressing an EBP50 mutant defective in serine 347/348 phosphorylation did not undergo apoptosis in suspension culture. These studies reveal a signaling cascade in which different phosphorylation states and subcellular localization of EBP50 regulate Rac1 function.

| S-EPMC3354064 | biostudies-literature

miR-29b negatively regulates MMP2 to impact gastric cancer development by suppress gastric cancer cell migration and tumor growth.

Project description:MicroRNAs (miRNAs) are important regulators and associated with the development of many different types of cancer, including gastric cancer. However, their pathophysiologic role and their relevance to tumorigenesis, invasion and metastasis are still unknown. In our current study, we performed microRNA array and found that 28 of miRNAs were differentially expressed in INF type of gastric cancer. Among 28 miRNAs, miR-29b was one of the most significantly down-regulated miRNA. Further bioinformatics analysis showed that MMP2 was a potential target of miR-29b. Interestingly, luciferase analysis showed that miR-29b negatively regulates MMP2 by binding with the miRNA response element (MRE) on the 3'UTR of MMP2. In addition, overexpression of miR-29b significantly decreased the mRNA and protein level of MMP2 and the activity of MMP2 to suppress gastric cancer cell migration. Moreover, lentivirus mediated overexpression of miR-29b dramatically suppressed the ability of BGC823 cells to form colonies in vitro and their ability to develop tumor in vivo in nude mice. Finally, our qPCR and western blot analysis showed that miR-29b was significantly reduced in clinical gastric cancer tissue, whereas MMP2 protein was significantly up-regulated, suggesting that this aberrant down-regulation of miR-29b might be associated with the abnormal regulation of MMP2 and the development of gastric cancer. Significant apparent was also found between miR-29b expression and TNM staging, lymph node status, tumor differentiation and Ming classification. Together, our data suggest an important regulatory role of miR-29b in the development of gastric cancer. Thus, miR-29b and MMP2 might be important diagnostic or therapeutic targets for human tumor diseases.

| S-EPMC6216010 | biostudies-literature

NF1-RAC1 axis regulates migration of the melanocytic lineage.

Project description:Metastases's spreading is the main cause of mortality for advanced stage cancer patients, including melanoma. The formation of metastases is favored by enhanced migratory and invasive capacities of tumor cells. Tumor suppressor gene NF1 is a negative regulator of RAS and its deregulation plays an important role in several aspects of melanoma transformation and progression. However, very little is described about the role of NF1 in cellular migration and invasion. In this study, our results show on the one hand, that the loss of NF1 expression delays migration of human melanoblasts via a RAC1-dependent mechanism. On the other hand, our data indicate that NF1 loss in melanoma cells is enhancing migration, intravasation and metastases formation in vivo. Moreover, not only this phenotype is associated with an upregulation of PREX1 but also patient-derived melanoma samples with low NF1 expression present increased levels of PREX1. In sum, our study brings new elements on the mechanism controlling cellular migration in the context of NF1 loss. These data are of prime interest to improve treatment strategies against all NF1-mutated tumors, including this subtype of melanoma.

| S-EPMC7484592 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data