Small GTPases最新文献_第10页

Endothelial RhoB and RhoC are dispensable for leukocyte diapedesis and for maintaining vascular integrity during diapedesis. 内皮RhoB和RhoC对于白细胞渗出和在渗出过程中维持血管完整性是必不可少的。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2018-01-29 DOI: 10.1080/21541248.2017.1377815

Lilian Schimmel, Aafke de Ligt, Simon Tol, Vivian de Waard, Jaap D van Buul

{"title":"Endothelial RhoB and RhoC are dispensable for leukocyte diapedesis and for maintaining vascular integrity during diapedesis.","authors":"Lilian Schimmel, Aafke de Ligt, Simon Tol, Vivian de Waard, Jaap D van Buul","doi":"10.1080/21541248.2017.1377815","DOIUrl":"https://doi.org/10.1080/21541248.2017.1377815","url":null,"abstract":"Active remodeling of the actin cytoskeleton in endothelial cells is necessary for allowing leukocytes to cross the barrier during the process of transendothelial migration (TEM). Involvement of RhoGTPases to regulate actin organization is inevitable, and we recently reported on the local function of RhoA in limiting vascular leakage during leukocyte TEM. As a follow-up we investigated here the possible involvement of two other closely-related GTPases; RhoB and RhoC, in regulating leukocyte TEM and vascular barrier maintenance. Physiological flow experiments showed no substantial involvement of either endothelial RhoB or RhoC in neutrophil adhesion and transmigration efficiency. Besides neutrophil TEM, we did not observe a role for endothelial RhoB or RhoC in limiting vascular leakage in both inflammatory conditions and during TEM. In conclusion, endothelial RhoB and RhoC are both dispensable for regulating leukocyte diapedesis and for maintaining vascular barrier function under inflammatory conditions and during leukocyte diapedesis.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":"11 3","pages":"225-232"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2017.1377815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35556503","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: 6

Ral function in muscle is required for flight maintenance in Drosophila. 果蝇的飞行维持需要肌肉中的Ral功能。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2017-12-28 DOI: 10.1080/21541248.2017.1367456

Shlesha Richhariya, Gaiti Hasan

引用次数: 1

Overexpression of YPT6 restores invasive filamentous growth and secretory vesicle clustering in a Candida albicans arl1 mutant. 在白色念珠菌arl1突变体中，过表达YPT6可恢复侵入性丝状生长和分泌囊泡聚集。

Small GTPases Pub Date : 2020-05-01 Epub Date: 2017-11-29 DOI: 10.1080/21541248.2017.1378157

Rohan Wakade, Hayet Labbaoui, Danièle Stalder, Robert A Arkowitz, Martine Bassilana

引用次数: 13

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":"11 3","pages":"155-159"},"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":"11 3","pages":"180-185"},"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":"11 3","pages":"194-203"},"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":"11 3","pages":"220-224"},"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