Coupling receptor tyrosine kinases to Rho GTPases--GEFs what's the link.


:Rho GTPases are molecular switches involved in the regulation of many cellular processes. This review summarizes work examining how stimulation of receptor tyrosine kinases (RTKs) leads to the activation of Rho guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. The collective findings strongly suggest that RTK signaling to Rho proteins is a general signal transduction mechanism, like RTK mediated activation of phosphatidyl inositol 3-kinase, phospholipase Cgamma, and the mitogen activated protein kinase (MAPK) pathway. More than half of the 58 known human RTKs activate at least one Rho family member. Likewise, 16 Rho GEFs directly interact with and/or are phosphorylated by a RTK. The specificity of receptor tyrosine kinase/Rho GEF signaling seems to be somewhat promiscuous. There several cases where multiple RTKs activate the same Rho GEF and where a single RTK can activate multiple Rho GEFs. Expression analysis indicates that the average human tissue contains transcripts for 33 RTKs, 34 Rho GEFs, and 14 Rho GTPases with each tissue containing a unique complement of these proteins. Given the promiscuity of RTKs for Rho GEFs, Rho GEFs for Rho GTPases, and the large number of these proteins expressed in cells, a complex combinatorial network of proteins in these families may contribute to coding specific signals and cell responses from RTKs.


Cell Signal


Cellular signalling


Schiller MR




Has Abstract


2006-11-01 00:00:00














  • Function and evolution of ubiquitous bacterial signaling adapter phosphopeptide recognition domain FHA.

    abstract::Forkhead-associated domain (FHA) is a phosphopeptide recognition domain embedded in some regulatory proteins. With similar fold type to important eukaryotic signaling molecules such as Smad2 and IRF3, the role of bacterial FHA domain is intensively pursued. Reported bacterial FHA domain roles include: regulation of gl...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Weiling H,Xiaowen Y,Chunmei L,Jianping X

    更新日期:2013-03-01 00:00:00

  • Different phosphorylated forms of inositolphosphate glycan could be involved in the transforming growth factor-beta 1 (TGF-beta 1) signalling pathway.

    abstract::Labelling with [3H]glucosamine was used to prepare a transforming growth factor-beta 1 (TGF-beta 1)-sensitive glycosylphosphatidylinositol (GPI) from monolayer cultures of rabbit articular chondrocytes (RAC), which may be involved in control of the cell cycle. The polar headgroup of this glycosylphosphatidylinositol w...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Vivien D,Bogdanowicz P,Boumediene K,Martiny L,Haye B,Pujol JP

    更新日期:1994-02-01 00:00:00

  • Insight into the therapeutic aspects of 'Zeta-Chain Associated Protein Kinase 70 kDa' inhibitors: a review.

    abstract::Zeta-Chain Associated Protein Kinase 70 kDa (ZAP-70), a member of Syk family (non-receptor protein tyrosine kinase family), has an imperative function in the immune cell signaling in T cells. Its role in T-cell development has been established by the severe combined immune deficiency syndrome in ZAP-70 deficient human...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Kaur M,Singh M,Silakari O

    更新日期:2014-11-01 00:00:00

  • Dephosphorylation of Fas-ligand and caveolin-1 is a prerequisite step in Fas-ligand - caveolin-1 complex formation and cell death stimulation.

    abstract::Fas-ligand/CD178 belongs to the TNF family proteins and is the well-characterized inducer of cell death. We showed previously that the interaction of Fas-ligand and caveolin-1 is necessary for Fas-ligand translocation to rafts, and the subsequent induction of Fas-ligand-dependent cell death. Both molecules can undergo...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Glukhova XA,Trizna JA,Proussakova OV,Gogvadze VG,Beletsky IP

    更新日期:2020-06-01 00:00:00

  • Reactive oxygen species in the tumor niche triggers altered activation of macrophages and immunosuppression: Role of fluoxetine.

    abstract::Macrophages are projected as one of the key players responsible for the progression of cancer. Classically activated (M1) macrophages are pro-inflammatory and have a central role in host defense, while alternatively activated (M2) macrophages are associated with immunosuppression. Macrophages residing at the site of n...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Ghosh S,Mukherjee S,Choudhury S,Gupta P,Adhikary A,Baral R,Chattopadhyay S

    更新日期:2015-07-01 00:00:00

  • Cbl: complex formation and functional implications.

    abstract::Chbl, a 120-kDa proto-oncogene product, whose gene was first identified as part of a transforming gene of a murine retrovirus and whose expression is predominant in haematopoietic cells, consists of an amino-terminal transforming region, a zinc Ring finger, multiple proline-rich stretches, and several potential phosph...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Liu YC,Altman A

    更新日期:1998-06-01 00:00:00

  • GATA3 as a master regulator for interactions of tumor-associated macrophages with high-grade serous ovarian carcinoma.

    abstract::High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic cancer. Emerging evidence suggests that tumor-associated macrophages (TAMs) play an immunosuppressive role in the tumor microenvironment and promote tumor growth, angiogenesis, and metastasis in ovarian cancer. Therefore, targeting TAMs in pati...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: El-Arabey AA,Denizli M,Kanlikilicer P,Bayraktar R,Ivan C,Rashed M,Kabil N,Ozpolat B,Calin GA,Salama SA,Abd-Allah AR,Sood AK,Lopez-Berestein G

    更新日期:2020-04-01 00:00:00

  • MyD88, IRAK1 and TRAF6 knockdown in human chondrocytes inhibits interleukin-1-induced matrix metalloproteinase-13 gene expression and promoter activity by impairing MAP kinase activation.

    abstract::Interleukin-1 (IL-1) is the major prototypic proinflammatory cytokine that stimulates degradation of cartilage in arthritis by inducing prominent collagen II-degrading matrix metalloproteinase-13 (MMP-13). Nothing is known about the involvement of adaptor proteins, MyD88, IRAK1 and TRAF6 in MMP-13 regulation. Here we ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Ahmad R,Sylvester J,Zafarullah M

    更新日期:2007-12-01 00:00:00

  • Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-kappaB/p300 binding in human synovial fibroblasts.

    abstract::Leptin, the adipocyte-secreted hormone that centrally regulates weight control, is known to function as an immunomodulatory regulator. We investigated the signaling pathway involved in IL-8 production caused by leptin in both rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OAS...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Tong KM,Shieh DC,Chen CP,Tzeng CY,Wang SP,Huang KC,Chiu YC,Fong YC,Tang CH

    更新日期:2008-08-01 00:00:00

  • Regulation of alternative splicing of CD44 in cancer.

    abstract::CD44 is a hyaluronan binding cell surface signal transducing receptor that influences motility, cell survival and proliferation as well as the formation of tumor microenvironment. CD44 contains two variable regions encoded by variable exons. Alternative splicing, which is often deregulated in cancer, can produce vario...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Prochazka L,Tesarik R,Turanek J

    更新日期:2014-10-01 00:00:00

  • Effects of long non-coding RNA LINC00667 on renal tubular epithelial cell proliferation, apoptosis and renal fibrosis via the miR-19b-3p/LINC00667/CTGF signaling pathway in chronic renal failure.

    abstract::The global prevalence of chronic renal failure (CRF) has significantly elevated with various reports indicating there to be a 10% worldwide rate. The functions of long non-coding RNAs (lncRNAs) and their deeper association with CRF at present remain poorly understood. Hence, the aim of the present study was to investi...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Chen W,Zhou ZQ,Ren YQ,Zhang L,Sun LN,Man YL,Wang ZK

    更新日期:2019-02-01 00:00:00

  • Activin induces hepatocyte cell growth arrest through induction of the cyclin-dependent kinase inhibitor p15INK4B and Sp1.

    abstract::In this report, we examined the role of activin in the regulation of cell growth inhibition of human hepatocarcinoma cells. Using RNase protection assay for various cell cycle regulators and Western blotting experiments, we show that activin treatment of HepG2 cells leads to increased gene expression of the cyclin-dep...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Ho J,de Guise C,Kim C,Lemay S,Wang XF,Lebrun JJ

    更新日期:2004-06-01 00:00:00

  • Starvation of a clonal osteoblast-like cell line, MOB 3-4-F2, down-regulates prostaglandin E2 receptors but increases cAMP response to prostaglandin E2.

    abstract::Prostaglandin E2 (PGE2) stimulated cAMP production in the MOB 3-4-F2 cell line, a subclone of the osteoblast-like MOB 3-4 cell line. After being cultured in alpha-minimum essential medium supplemented with 10% heat-inactivated foetal calf serum (HIFCS), cells responded to PGE2 (greater than or equal to 50 ng/ml) with ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Kawase T,Orikasa M,Suzuki A

    更新日期:1991-01-01 00:00:00

  • Capsaicin induces cytotoxicity in pancreatic neuroendocrine tumor cells via mitochondrial action.

    abstract::Capsaicin (CAP), the pungent ingredient of chili peppers, inhibits growth of various solid cancers via TRPV1 as well as TRPV1-independent mechanisms. Recently, we showed that TRPV1 regulates intracellular calcium level and chromogranin A secretion in pancreatic neuroendocrine tumor (NET) cells. In the present study, w...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Skrzypski M,Sassek M,Abdelmessih S,Mergler S,Grötzinger C,Metzke D,Wojciechowicz T,Nowak KW,Strowski MZ

    更新日期:2014-01-01 00:00:00

  • Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity.

    abstract::Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in development for chronic inflammatory disorders, and has shown efficacy in psoriasis, psoriatic arthropathies, and Behçet's syndrome. In March 2014, the US Food and Drug Administration approved apremilast for the treatment of adult patien...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Schafer PH,Parton A,Capone L,Cedzik D,Brady H,Evans JF,Man HW,Muller GW,Stirling DI,Chopra R

    更新日期:2014-09-01 00:00:00

  • Factors affecting prostacyclin receptor agonist efficacy in different cell types.

    abstract::Octimibate and related nonprostanoid prostacyclin mimetics are partial agonists displaying highly tissue-specific responses. Octimibate demonstrated considerably greater efficacy for stimulation of adenylyl cyclase activity in Chinese hamster ovary cells transiently expressing mouse prostacyclin receptors (mIP-CHO cel...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Kam Y,Chow KB,Wise H

    更新日期:2001-11-01 00:00:00

  • Homeostatic interactions between MEKK3 and TAK1 involved in NF-kappaB signaling.

    abstract::Several members of the mitogen-activated protein kinase kinase kinase (MAP3K) family including MEKK3 and TGFbeta-activating kinase (TAK1) play nonredundant roles in activation of the NF-kappaB transcription factor. However, the mechanism by which MEKK3 mediates NF-kappaB signaling is not fully understood. In this repo...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Di Y,Li S,Wang L,Zhang Y,Dorf ME

    更新日期:2008-04-01 00:00:00

  • Regulation of cellular functions by the ERK5 signalling pathway.

    abstract::Extracellular-regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase (MAPK) regulated by a wide range of mitogens and cellular stresses. Since its cloning in 1995, the lack of biological tools, including antibodies and specific inhibitors, have made it one of the least studied MAPK subfamilies. The di...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Wang X,Tournier C

    更新日期:2006-06-01 00:00:00

  • Selective proteolysis by matrix metalloproteinases of photo-oxidised dermal extracellular matrix proteins.

    abstract::Photodamage in chronically sun-exposed skin manifests clinically as deep wrinkles and histologically as extensive remodelling of the dermal extracellular matrix (ECM) and in particular, the elastic fibre system. We have shown previously that loss of fibrillin microfibrils, a key elastic fibre component, is a hallmark ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Hibbert SA,Watson REB,Griffiths CEM,Gibbs NK,Sherratt MJ

    更新日期:2019-02-01 00:00:00

  • Non-canonical functions of RGS proteins.

    abstract::Regulators of G protein signalling (RGS) proteins are united into a family by the presence of the RGS domain which serves as a GTPase-activating protein (GAP) for various Galpha subunits of heterotrimeric G proteins. Through this mechanism, RGS proteins regulate signalling of numerous G protein-coupled receptors. In a...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Sethakorn N,Yau DM,Dulin NO

    更新日期:2010-09-01 00:00:00

  • CD40 mediated human cholangiocyte apoptosis requires JAK2 dependent activation of STAT3 in addition to activation of JNK1/2 and ERK1/2.

    abstract::CD40 is critically involved in Fas-mediated cholangiocyte apoptosis during liver inflammation, but the underlying signalling events are poorly understood. Our recent work implicated AP-1 in CD40-induced cholangiocyte apoptosis, but suggested involvement of other signalling pathways. Because STAT3 has been implicated i...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Ahmed-Choudhury J,Williams KT,Young LS,Adams DH,Afford SC

    更新日期:2006-04-01 00:00:00

  • Insulin activates caspase-3 by a phosphatidylinositol 3'-kinase-dependent pathway.

    abstract::Activation of the caspase proteases by c-Jun N-terminal kinase 1 (JNK1) has been proposed as a mechanism of apoptotic cell death. Here we report that insulin activates caspase-3 by a pathway requiring phosphatidylinositol 3'-kinase (PI3-kinase). JNK1 assays demonstrated that insulin treatment of myeloma cells induced ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Godbout JP,Cengel KA,Cheng SL,Minshall C,Kelley KW,Freund GG

    更新日期:1999-01-01 00:00:00

  • Interleukin-1-induced activation of the small GTPase Rac1 depends on receptor internalization and regulates gene expression.

    abstract::Interleukin 1 (IL-1) triggers the internalization of its cognate receptor from the plasma membrane. We recently demonstrated that this internalization is of critical importance for the IL-1-induced gene expression. In this study we report that the IL-1-induced activation of the small GTPase Rac1 requires receptor endo...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Windheim M,Hansen B

    更新日期:2014-01-01 00:00:00

  • TMC8 (EVER2) attenuates intracellular signaling by Zn2+ and Ca2+ and suppresses activation of Cl- currents.

    abstract::Eight paralogue members form the family of transmembrane channel-like (TMC) proteins that share considerable sequence homology to anoctamin 1 (Ano1, TMEM16A). Ano1 is a Ca(2+) activated Cl(-) channel that is related to head and neck cancer, often caused by human papilloma virus (HPV) infection. Mutations in TMC 6 and ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Sirianant L,Ousingsawat J,Tian Y,Schreiber R,Kunzelmann K

    更新日期:2014-12-01 00:00:00

  • Interaction between TCL1 and Epac1 in the activation of Akt kinases in plasma membranes and nuclei of 8-CPT-2-O-Me-cAMP-stimulated macrophages.

    abstract::Epac1 is a cAMP-stimulated guanine exchange factor that activates Rap1. The protein product of the T cell leukemia 1 (TCL1) proto-oncogene binds to Akt enhancing its kinase activity. TCL1 and Epac promote cellular proliferation because of their activating effects on Akt. Employing macrophages, we have studied the mech...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Misra UK,Kaczowka SJ,Pizzo SV

    更新日期:2008-01-01 00:00:00

  • Spatial and temporal activation of the small GTPases RhoA and Rac1 by the netrin-1 receptor UNC5a during neurite outgrowth.

    abstract::Netrin-1 attracts or repels growing axons during development. The UNC5 receptors mediate the repulsive response, either alone or in complex with DCC receptors. The signaling mechanisms activated by UNC5 are poorly understood. Here, we examined the role of Rho GTPases in UNC5a signaling. We found that UNC5a induced neu...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Picard M,Petrie RJ,Antoine-Bertrand J,Saint-Cyr-Proulx E,Villemure JF,Lamarche-Vane N

    更新日期:2009-12-01 00:00:00

  • Low intensity pulsed ultrasound accelerates macrophage phagocytosis by a pathway that requires actin polymerization, Rho, and Src/MAPKs activity.

    abstract::Phagocytosis is an essential event in the complex process of tissue repair. Here we examined the effect of low intensity pulsed ultrasound (US), which promotes fracture and wound healing, on phagocytosis by mouse macrophage cell line J774A.1 and human monocyte-derived macrophages. First, 10 to 40 min low intensity pul...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Zhou S,Bachem MG,Seufferlein T,Li Y,Gross HJ,Schmelz A

    更新日期:2008-04-01 00:00:00

  • G proteins are involved in the suppression of collagen alpha 1 (I) gene expression in cultured rat hepatic stellate cells.

    abstract::We analyse the role of the G proteins in regulating collagen gene expression by measuring collagen alpha 1(I) mRNA levels in cultured hepatic stellate cells in basal conditions and after stimulating or inhibiting the major intracellular signalling pathways. Stimulation of Gs protein and adenylyl cyclase or the additio...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Solís-Herruzo JA,Hernández I,De la Torre P,García I,Sánchez JA,Fernández I,Castellano G,Muñoz-Yagüe T

    更新日期:1998-03-01 00:00:00

  • Inter- and intra-cellular mechanism of NF-kB-dependent survival advantage and clonal expansion of radio-resistant cancer cells.

    abstract::Understanding the underlying mechanism by which cancer cells acquire resistance to radiation and favorably selected for its clonal expansion will provide molecular insight into tumor recurrence at the treatment site. In the present study, we investigated the molecular mechanisms prompted in MCF-7 breast cancer cells i...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Yu H,Aravindan N,Xu J,Natarajan M

    更新日期:2017-02-01 00:00:00

  • Effects of retinoic acid on signalling by prostaglandin E2 in osteoblast-like cells.

    abstract::We investigated the effects of retinoic acid (RA) on the signalling pathways by prostaglandin E2 (PGE2) in osteoblast-like MC3T3-E1 cells. The pretreatment with RA significantly inhibited the formation of inositol phosphates induced by 10 microM PGE2 in a dose-dependent manner in the range between 0.1 nM and 0.1 micro...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Kotoyori J,Tokuda H,Oiso Y,Kozawa O

    更新日期:1993-07-01 00:00:00