Transformation by the Rho-specific guanine nucleotide exchange factor Dbs requires ROCK I-mediated phosphorylation of myosin light chain. 2006

Zhuoming Liu, and Elena V Kostenko, and Gwendolyn M Mahon, and Oyenike O Olabisi, and Ian P Whitehead
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.

Dbs was identified in a cDNA-based expression screen for sequences that can cause malignant growth when expressed in murine fibroblasts. In previous studies we have shown that Dbs is a Rho-specific guanine nucleotide exchange factor that can activate RhoA and/or Cdc42 in a cell-specific manner. In this current study we have used a combination of genetic and pharmacological approaches to examine the relative contributions of RhoA x PRK and RhoA x ROCK signaling to Dbs transformation. Our analysis indicates that ROCK is activated in Dbs-transformed cells and that Dbs transformation is dependent upon ROCK I activity. In contrast, there appears to be no requirement for PRK activation in Dbs transformation. Dbs transformation is also associated with increased phosphorylation of myosin light chain and stress fiber formation, both of which occur in a ROCK-dependent manner. Suppression of myosin light chain expression by small interfering RNAs impairs Dbs focus formation, thus establishing a direct link between actinomyosin contraction and Rho-specific guanine nucleotide exchange factor transformation.

UI MeSH Term Description Entries
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D017346 Protein Serine-Threonine Kinases A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D047908 Intracellular Signaling Peptides and Proteins Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors. Intracellular Signaling Peptides,Intracellular Signaling Proteins,Peptides, Intracellular Signaling,Proteins, Intracellular Signaling,Signaling Peptides, Intracellular,Signaling Proteins, Intracellular
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054460 rho-Associated Kinases A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES. rho-Associated Kinase,ROCK Protein Kinases,ROCK-I Protein Kinase,ROCK-II Protein Kinase,ROK Kinase,p160 rhoA-Binding Kinase ROKalpha,p160ROCK,rho-Associated Coiled-Coil Containing Protein Kinase 1,rho-Associated Coiled-Coil Containing Protein Kinase 2,rho-Associated Coiled-Coil Kinase,rho-Associated Kinase 1,rho-Associated Kinase 2,rho-Associated Kinase alpha,rho-Associated Kinase beta,rho-Associated Protein Kinase alpha,rho-Associated Protein Kinase beta,rho-Kinase,Coiled-Coil Kinase, rho-Associated,Protein Kinases, ROCK,ROCK I Protein Kinase,ROCK II Protein Kinase,p160 rhoA Binding Kinase ROKalpha,rho Associated Coiled Coil Containing Protein Kinase 1,rho Associated Coiled Coil Containing Protein Kinase 2,rho Associated Coiled Coil Kinase,rho Associated Kinase,rho Associated Kinase 1,rho Associated Kinase 2,rho Associated Kinase alpha,rho Associated Kinase beta,rho Associated Kinases,rho Associated Protein Kinase alpha,rho Associated Protein Kinase beta,rho Kinase
D018994 Myosin Light Chains The smaller subunits of MYOSINS that bind near the head groups of MYOSIN HEAVY CHAINS. The myosin light chains have a molecular weight of about 20 KDa and there are usually one essential and one regulatory pair of light chains associated with each heavy chain. Many myosin light chains that bind calcium are considered "calmodulin-like" proteins. Myosin Alkali Light Chains,Myosin Alkali Light Chain,Myosin Essential Light Chain,Myosin Essential Light Chains,Myosin Light Chain,Myosin Regulatory Light Chain,Myosin Regulatory Light Chains,Light Chain, Myosin,Light Chains, Myosin
D020662 Guanine Nucleotide Exchange Factors Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS. GDP Exchange Factors,GDP-GTP Reversing Factors,Guanine Nucleotide Releasing Factors,GDP Dissociation Factor,GDP Dissociation Stimulators,GDP-GTP Exchange Protein,Guanine Nucleotide Exchange Factor,Guanine-Nucleotide-Releasing Factor,Exchange Factors, GDP,Factors, GDP Exchange,Factors, GDP-GTP Reversing,GDP GTP Exchange Protein,GDP GTP Reversing Factors,Guanine Nucleotide Releasing Factor,Reversing Factors, GDP-GTP
D034741 RNA, Small Interfering Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions. RNA, Scan,Repeat-Associated siRNA,Scan RNA,Small Scan RNA,Trans-Acting siRNA,siRNA,siRNA, Repeat-Associated,siRNA, Trans-Acting,Short Hairpin RNA,Short Interfering RNA,Small Hairpin RNA,Small Interfering RNA,scnRNA,shRNA,tasiRNA,Hairpin RNA, Short,Hairpin RNA, Small,Interfering RNA, Short,Interfering RNA, Small,RNA, Short Hairpin,RNA, Short Interfering,RNA, Small Hairpin,RNA, Small Scan,Repeat Associated siRNA,Scan RNA, Small,Trans Acting siRNA,siRNA, Repeat Associated,siRNA, Trans Acting

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