Small GTPases最新文献_第10页

Crosstalk between WIP and Rho family GTPases. WIP与Rho家族gtp酶之间的串扰。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2018-01-29 DOI: 10.1080/21541248.2017.1390522

Inés M Antón, Carla Gómez-Oro, Sergio Rivas, Francisco Wandosell

引用次数: 6

FER mediated HGF-independent regulation of HGFR/MET activates RAC1-PAK1 pathway to potentiate metastasis in ovarian cancer. FER介导的HGFR/MET不依赖于hgf的调控激活了RAC1-PAK1通路，从而增强了卵巢癌的转移。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2018-01-24 DOI: 10.1080/21541248.2017.1379931

Gaofeng Fan

{"title":"FER mediated HGF-independent regulation of HGFR/MET activates RAC1-PAK1 pathway to potentiate metastasis in ovarian cancer.","authors":"Gaofeng Fan","doi":"10.1080/21541248.2017.1379931","DOIUrl":"https://doi.org/10.1080/21541248.2017.1379931","url":null,"abstract":"Uncontrolled metastasis significantly contributes to high lethality of patients suffering from ovarian cancer. To date, the detailed molecular mechanisms which account for ovarian tumor cell spreading and metastasis remain largely unknown. In a recent study, we have demonstrated that aberrantly high expression of the non-receptor tyrosine kinase FER is responsible for ovarian tumor cell metastasis both in vitro and in vivo. Mechanistically, we indentified Hepatocyte Growth Factor Receptor HGFR/MET as a novel substrate of FER, and through which the kinase FER modulates ovarian cancer cell motility and invasiveness in a ligand-independent manner. We also observed aberrantly high expression of PAK1 kinase in cancer cells, and RNAi-mediated knockdown of FER kinase inactivated the RAC1-PAK1 signaling pathway and decreased metastatic potential of CAOV4 ovarian cancer cells. Overall, our study revealed a previously uncharacterized, pro-metastatic role of the kinase FER in ovarian cancer through the MET-RAC1-PAK1 pathway. Further efforts are essential to investigating beneficial outcomes towards targeting the RAC1-PAK1 signaling pathway in reducing metastatic burden of this deadly disease.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2017.1379931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35571872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

RAS ubiquitylation modulates effector interactions. RAS泛素化调节效应物相互作用。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2017-11-29 DOI: 10.1080/21541248.2017.1371267

Ryan Thurman, Edhriz Siraliev-Perez, Sharon L Campbell

{"title":"RAS ubiquitylation modulates effector interactions.","authors":"Ryan Thurman, Edhriz Siraliev-Perez, Sharon L Campbell","doi":"10.1080/21541248.2017.1371267","DOIUrl":"https://doi.org/10.1080/21541248.2017.1371267","url":null,"abstract":"RAS proteins function as molecular switches that regulate cellular growth by cycling between active GTP- and inactive GDP bound states. While RAS activity is modulated by factors (guanine nucleotide exchange and GTPase activating proteins) that control levels of active Ras-GTP, RAS proteins also undergo a number of post-translational modifications that regulate their function. One such modification is ubiquitylation. Monoubiquitylation of KRAS at lysine 147 (mUbRAS) enhances Ras activation and promotes signaling through the RAF and Phosphoinositide 3-Kinase (PI3K) signaling pathways. We have previously shown that mUbRAS leads to activation of RAS through a defect in GTPase activating protein (GAP) mediated downregulation, similar to the action of most oncogenic mutations. Consistent with these findings, we now show that mUbRASimpairsRAS binding to the p120 GAP catalytic domain. Mutations in activated G12V RAS that prevent ubiquitylaton at 147 show a decrease in tumorigenesis, suggesting that in addition to activating KRAS, monoubiquitylation at this site may promote downstream signaling and transformation. To investigate whether mUbRAS alters RAS effector interactions, we chemically ubiquitylated KRAS at residue 147 and characterized binding of mUbRAS to RAS binding domains (RBDs) from three distinct downstream effectors that play key roles in RAS-mediated transformation. Results from these studies show a decrease in binding of mUbRAS (7-10-fold) relative to the CRAF RAS Binding Domain (RBD), the catalytic subunit of Phosphoinositide 3-Kinase catalytic gamma (PI3Kcγ) and RALGDS RBD. Intriguingly, we find that mUbRAS shows greatly enhanced (> 40-fold) binding to the CRAF RBD when bound to GDP. These findings, taken together, suggest that mUbRASmay promoteactivation of RAS through a GAP defect, and facilitate RAF association and MAPK signaling in a nucleotide independent manner.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2017.1371267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35650113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

GRAF3 serves as a blood volume-sensitive rheostat to control smooth muscle contractility and blood pressure. GRAF3 是对血容量敏感的流变调节器，可控制平滑肌收缩力和血压。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2018-01-07 DOI: 10.1080/21541248.2017.1375602

Xue Bai, Kevin Mangum, Masao Kakoki, Oliver Smithies, Christopher P Mack, Joan M Taylor

{"title":"GRAF3 serves as a blood volume-sensitive rheostat to control smooth muscle contractility and blood pressure.","authors":"Xue Bai, Kevin Mangum, Masao Kakoki, Oliver Smithies, Christopher P Mack, Joan M Taylor","doi":"10.1080/21541248.2017.1375602","DOIUrl":"10.1080/21541248.2017.1375602","url":null,"abstract":"Vascular resistance is a major determinant of BP and is controlled, in large part, by RhoA-dependent smooth muscle cell (SMC) contraction within small peripheral arterioles and previous studies from our lab indicate that GRAF3 is a critical regulator of RhoA in vascular SMC. The elevated contractile responses we observed in GRAF3 deficient vessels coupled with the hypertensive phenotype provided a mechanistic link for the hypertensive locus recently identified within the GRAF3 gene. On the basis of our previous findings that the RhoA signaling axis also controls SMC contractile gene expression and that GRAF3 expression was itself controlled by this pathway, we postulated that GRAF3 serves as an important counter-regulator of SMC phenotype. Indeed, our new findings presented herein indicate that GRAF3 expression acts as a pressure-sensitive rheostat to control vessel tone by both reducing calcium sensitivity and restraining expression of the SMC-specific contractile proteins that support this function. Collectively, these studies highlight the potential therapeutic value of GRAF3 in the control of human hypertension.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2017.1375602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35569009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

AMPK and autophagy control embryonic elongation as part of a RhoA-like morphogenic program in nematode. 在线虫中，AMPK和自噬作为rhoa样形态发生程序的一部分控制胚胎伸长。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2017-11-25 DOI: 10.1080/21541248.2017.1372868

Emmanuel Martin, Grégoire Bonnamour, Sarah Jenna

引用次数: 2

A novel prenyl-polybasic domain code determines lipid-binding specificity of the K-Ras membrane anchor. 一种新的聚戊烯基结构域代码决定了K-Ras膜锚定的脂质结合特异性。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2018-01-15 DOI: 10.1080/21541248.2017.1379583

Yong Zhou, John F Hancock

{"title":"A novel prenyl-polybasic domain code determines lipid-binding specificity of the K-Ras membrane anchor.","authors":"Yong Zhou, John F Hancock","doi":"10.1080/21541248.2017.1379583","DOIUrl":"https://doi.org/10.1080/21541248.2017.1379583","url":null,"abstract":"Ras proteins must localize to the plasma membrane (PM) for biological function. The membrane anchor of the K-Ras4B isoform comprises a farnesylated and methylated C-terminal cysteine together with an adjacent hexa-lysine polybasic domain (PBD). Traditionally, polybasic sequences have been thought to interact electrostatically with negatively charged membranes showing no specificity for anionic lipid head groups. By contrast we recently showed that the K-Ras membrane anchor actually exhibits a very high degree of specificity for phosphatidylserine (PtdSer). The selectivity for PtdSer is determined by a combinatorial code comprising the PBD sequence plus the prenyl anchor. Lipid binding specificity is therefore altered by PBD point mutations that in turn modulate signaling output. For example, mutating Lys177 or Lys178 to glutamine switches K-Ras4B lipid affinity from PtdSer to phosphoinositol 4,5-bisphosphate (PIP2). Changing the lipid anchor from farnesyl to geranylgeranyl or the PBD lysines to arginines also changes lipid binding specificity. All-atom molecular dynamics simulations reveal the structural basis for these K-Ras anchor lipid-binding preferences. Here we examine the PM interactions of a series of geranylgeranylated PBD mutants and provide further evidence that the precise PBD sequence and prenyl lipid determines lipid sorting specificity of the K-Ras anchor and hence biological function.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2017.1379583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35655260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

Post-translational modifications: How to modulate Rab7 functions. 翻译后修饰:如何调节Rab7的功能。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2018-01-02 DOI: 10.1080/21541248.2017.1387686

Graziana Modica, Stephane Lefrancois

引用次数: 11

MYC leads the way. MYC引领潮流。

Small GTPases Pub Date : 2020-03-01 Epub Date: 2017-11-25 DOI: 10.1080/21541248.2017.1364821

Niranjan Venkateswaran, Maralice Conacci-Sorrell

引用次数: 25

The ROCK isoforms differentially regulate the morphological characteristics of carcinoma cells. ROCK亚型对癌细胞的形态特征有差异调节。

Small GTPases Pub Date : 2020-03-01 Epub Date: 2017-09-18 DOI: 10.1080/21541248.2017.1341366

Rachel J Jerrell, Mitchell J Leih, Aron Parekh

引用次数: 13

Small GTPases orchestrate cell-cell communication during collective cell movement. 在集体细胞运动过程中，小的gtpase协调细胞间的通信。

Small GTPases Pub Date : 2020-03-01 Epub Date: 2017-12-17 DOI: 10.1080/21541248.2017.1366965

Anne Combedazou, Stéphanie Gayral, Nathalie Colombié, Anne Fougerat, Muriel Laffargue, Damien Ramel

{"title":"Small GTPases orchestrate cell-cell communication during collective cell movement.","authors":"Anne Combedazou, Stéphanie Gayral, Nathalie Colombié, Anne Fougerat, Muriel Laffargue, Damien Ramel","doi":"10.1080/21541248.2017.1366965","DOIUrl":"https://doi.org/10.1080/21541248.2017.1366965","url":null,"abstract":"Collective cell migration is a critical mechanism involved in cell movement during various physiological and pathological processes such as angiogenesis and metastasis formation. During collective movement, cells remain functionally connected and can coordinate individual cell behaviors to ensure efficient migration. A cell-cell communication process ensures this complex coordination. Although the mechanisms regulating cell-cell communication remain unclear, recent findings indicate that it is based on acto-myosin cytoskeleton tension transmission from cell to cell through adherens junctions. As for single cell migration, small GTPases of the Rho and Rab families have been shown to be critical regulators of collective motion. Here, we discuss our current understanding on how these small GTPases are themselves regulated and how they control cell-cell communication during collective migration. Moreover, we also shed light on the key role of cell-cell communication and RhoGTPases in the physiological context of endothelial cell migration during angiogenesis.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2017.1366965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35418294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16