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














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    abstract::Signal transducers and activators of transcription 3 (STAT3) is reported to regulate cell proliferation, survival, and differentiation, and thus plays a central role in development and carcinogenesis. Accumulating evidence demonstrated the involvement of cellular Src (c-Src) tyrosine kinase in the activation of STAT3....

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Wang Y,Liu S,Jiang G,Zhai W,Yang L,Li M,Chang Z,Zhu B

    更新日期:2020-11-01 00:00:00

  • Cytidine monophosphate kinase is inhibited by the TGF-β signalling pathway through the upregulation of miR-130b-3p in human epithelial ovarian cancer.

    abstract::Cytidine monophosphate kinase (CMPK), a member of the nucleoside monophosphate kinase family, plays an important role in the biosynthesis of nucleoside metabolism, DNA repair and tumour development. In this study, we demonstrated for the first time that CMPK was overexpressed in human ovarian epithelial borderline and...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Zhou D,Zhang L,Sun W,Guan W,Lin Q,Ren W,Zhang J,Xu G

    更新日期:2017-07-01 00:00:00

  • GSK3beta inhibition promotes melanogenesis in mouse B16 melanoma cells and normal human melanocytes.

    abstract::Glycogen synthase kinase 3beta (GSK3beta) is implicated in many biological events, including embryonic development, cell differentiation, apoptosis, and the insulin response. GSK3beta also plays a key role in the Wnt/beta-catenin pathway. The master regulator of the pigmentation microphthalmia-associated transcription...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Bellei B,Flori E,Izzo E,Maresca V,Picardo M

    更新日期:2008-10-01 00:00:00

  • DAPk1 inhibits NF-κB activation through TNF-α and INF-γ-induced apoptosis.

    abstract::Recent studies have shown DAPk as a molecular modulator induced by the second messenger, responsible for controlling cell destiny decisions, but the detailed mechanism mediating the role of DAPk1 during cell death is still not fully understood. In this present report, we attempted to characterize the effects of TNF-α ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Yoo HJ,Byun HJ,Kim BR,Lee KH,Park SY,Rho SB

    更新日期:2012-07-01 00:00:00

  • The Pyk2 FERM regulates Pyk2 complex formation and phosphorylation.

    abstract::The focal adhesion kinase Pyk2 integrates signals from cell adhesion receptors, growth factor receptors, and G-protein-coupled receptors leading to the activation of intracellular signaling pathways that regulate cellular phenotypes. The intrinsic mechanism for the activation of Pyk2 activity remains to be fully defin...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Riggs D,Yang Z,Kloss J,Loftus JC

    更新日期:2011-01-01 00:00:00

  • TMEPAI/PMEPA1 inhibits Wnt signaling by regulating β-catenin stability and nuclear accumulation in triple negative breast cancer cells.

    abstract::Transmembrane prostate androgen-induced protein (TMEPAI) is a type I transmembrane protein induced by several intracellular signaling pathways such as androgen, TGF-β, EGF, and Wnt signaling. It has been reported that TMEPAI functions to suppress TGF-β and androgen signaling but here, we report a novel function of TME...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Amalia R,Abdelaziz M,Puteri MU,Hwang J,Anwar F,Watanabe Y,Kato M

    更新日期:2019-07-01 00:00:00

  • Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells.

    abstract::We report here a direct modulation by mast cell tryptase of endothelial barrier function through activation of proteinase-activated receptor-2 (PAR-2). In cultured bovine aortic endothelial cells (BAECs), tryptase, trypsin and PAR-2 activating peptide impaired the barrier function as determined by the permeability of ...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Sendo T,Sumimura T,Itoh Y,Goromaru T,Aki K,Yano T,Oike M,Ito Y,Mori S,Nishibori M,Oishi R

    更新日期:2003-08-01 00:00:00

  • The last five amino acid residues at the C-terminus of PRK1/PKN is essential for full lipid responsiveness.

    abstract::PRK1/PKN is a member of the protein kinase C (PKC) superfamily of serine/threonine protein kinases. Despite its important role as a RhoA effector, limited information is available regarding how this kinase is regulated. We show here that the last seven amino acid residues at the C-terminus is dispensable for the catal...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Lim WG,Zhu Y,Wang CH,Tan BJ,Armstrong JS,Dokland T,Yang H,Zhu YZ,Teo TS,Duan W

    更新日期:2005-09-01 00:00:00

  • Regulation of the CCN genes by vitamin D: A possible adjuvant therapy in the treatment of cancer and fibrosis.

    abstract::The CCN family is composed of six cysteine-rich, modular, and conserved proteins whose functions span a variety of tissues and include cell proliferation, adhesion, angiogenesis, and wound healing. Roles for the CCN proteins throughout the entire body including the skin, kidney, brain, blood vessels, hematopoietic com...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Piszczatowski RT,Lents NH

    更新日期:2016-10-01 00:00:00

  • C5L2 is required for C5a-triggered receptor internalization and ERK signaling.

    abstract::C5L2 is a receptor that binds to C5a and belongs to the family of G protein-coupled receptors, but its role in physiological C5a-mediated responses remains under debate. Here we show that, like the canonical C5a receptor C5aR, C5L2 plays a pro-inflammatory role in a murine model of acute experimental colitis. We demon...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Hsu WC,Yang FC,Lin CH,Hsieh SL,Chen NJ

    更新日期:2014-07-01 00:00:00

  • Cellular signaling in pseudoxanthoma elasticum: an update.

    abstract::Pseudoxanthoma elasticum is an autosomal recessive genodermatosis with variable expression, due to mutations in the ABCC6 or ENPP1 gene. It is characterized by elastic fiber mineralization and fragmentation, resulting in skin, eye and cardiovascular symptoms. Significant advances have been made in the last 20 years wi...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Van Gils M,Nollet L,Verly E,Deianova N,Vanakker OM

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  • 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

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  • Roles of Axin in the Wnt signalling pathway.

    abstract::The Wnt signalling pathway is conserved in various species from worms to mammals, and plays important roles in development, cellular proliferation, and differentiation. The molecular mechanisms by which the Wnt signal regulates cellular functions are becoming increasingly well understood. Wnt stabilizes cytoplasmic be...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Kikuchi A

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  • 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.

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    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

  • The effects of N-ras oncogene expression on PDGF-BB stimulated responses in cultured mouse myoblasts.

    abstract::The role of the ras oncogene in the signalling pathway triggered by platelet-derived growth factor BB (PDGF-BB) has been investigated in a cell line which normally differentiates into myotubes. Following the activation of the N-ras oncogene, however, the cells proliferate and form foci. PDGF-BB stimulated the phosphor...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Zeytinoğlu H,Griffiths SL,Dawson AP,Gibson I

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  • Ligand activation of peroxisome proliferator-activated receptor-beta/delta(PPARbeta/delta) inhibits cell growth of human N/TERT-1 keratinocytes.

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    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Burdick AD,Bility MT,Girroir EE,Billin AN,Willson TM,Gonzalez FJ,Peters JM

    更新日期:2007-06-01 00:00:00

  • Cbl: complex formation and functional implications.

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    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

  • CIKS (Act1 or TRAF3IP2) mediates high glucose-induced endothelial dysfunction.

    abstract::Hyperglycemia-induced endothelial dysfunction is characterized by enhanced inflammatory cytokine and adhesion molecule expression, and endothelial-monocyte adhesion. The adapter molecule CIKS (connection to IKK and SAPK/JNK; also known as Act1 or TRAF3IP2) is an upstream regulator of NF-κB and AP-1, and plays a role i...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Venkatesan B,Valente AJ,Das NA,Carpenter AJ,Yoshida T,Delafontaine JL,Siebenlist U,Chandrasekar B

    更新日期:2013-01-01 00:00:00

  • Deregulation of Tpl2 and NF-kappaB signaling and induction of macrophage apoptosis by the anti-depressant drug lithium.

    abstract::Lithium is an anti-depressant drug that also possesses immunomodulatory functions. The anti-inflammatory effect of lithium is thought to involve activation of the transcription factor CREB, although the underlying mechanism is incompletely understood. We show here that in macrophages lithium stimulates Tpl2, a MAP kin...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Zhang M,Jin W,Zhou X,Yu J,Lee AJ,Sun SC

    更新日期:2009-04-01 00:00:00

  • Effect of H-ras proteins on the activity of polyphosphoinositide phospholipase C in HL60 membranes.

    abstract::The present study was undertaken to investigate whether purified ras proteins can affect the activity of polyphosphoinositide specific phospholipase C in a cell-free membrane system. For this purpose we used homogenous preparations of the proto-oncogenic (H-ras(gly 12)) and the oncogenic (H-ras(val 12)) forms of the h...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Cockcroft S,Bar-Sagi D

    更新日期:1990-01-01 00:00:00

  • CB₁ cannabinoid receptors promote maximal FAK catalytic activity by stimulating cooperative signaling between receptor tyrosine kinases and integrins in neuronal cells.

    abstract::Tyrosine phosphorylation (Tyr-P) of focal adhesion kinase (FAK) regulates FAK activation. Phosphorylated FAK Tyr 397 binds Src family kinases (Src), which in turn directly phosphorylate FAK Tyr 576/577 to produce maximal FAK enzymatic activity. CB₁ cannabinoid receptors (CB₁) are abundantly expressed in the nervous sy...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Dalton GD,Peterson LJ,Howlett AC

    更新日期:2013-08-01 00:00:00

  • Thrombin induces nestin expression via the transactivation of EGFR signalings in rat vascular smooth muscle cells.

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    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Huang YL,Shi GY,Lee H,Jiang MJ,Huang BM,Wu HL,Yang HY

    更新日期:2009-06-01 00:00:00

  • Apelin signalling: a promising pathway from cloning to pharmacology.

    abstract::The discovery of new signalling pathways is always followed by the development of pharmacological agents as drugs that can be used in the treatment of diseases resulting from a dysfunction of the signalling pathway in question. Apelin signalling plays a role in the central and peripheral regulation of the cardiovascul...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Masri B,Knibiehler B,Audigier Y

    更新日期:2005-04-01 00:00:00

  • CaMKIIδ interacts directly with IKKβ and modulates NF-κB signalling in adult cardiac fibroblasts.

    abstract::Calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) acts as a molecular switch regulating cardiovascular Ca2+ handling and contractility in health and disease. Activation of CaMKIIδ is also known to regulate cardiovascular inflammation and is reported to be required for pro-inflammatory NF-κB signalling. In this...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Martin TP,McCluskey C,Cunningham MR,Beattie J,Paul A,Currie S

    更新日期:2018-11-01 00:00:00

  • Constitutive and regulated secretion of epidermal growth factor and transforming growth factor-beta1 in MDA-MB-231 breast cancer cell line in 11-day cultures.

    abstract::Epidermal growth factor (EGF) and transforming growth factor type beta1 (TGF-beta1) exert opposite effects in most cells. A potential regulation between the two factors has been studied at a transcriptional level, but never at a protein level. MDA-MB-231 is a breast carcinoma cell line which possesses large quantities...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Martínez-Carpio PA,Mur C,Rosel P,Navarro MA

    更新日期:1999-10-01 00:00:00

  • Differential involvement of H- and K-Ras in Raf-1 activation determines the role of calmodulin in MAPK signaling.

    abstract::We have previously demonstrated that inhibition of calmodulin (CaM) and the concomitant reduction of PI3K interfere with H-Ras-mediated activation of Raf-1 [1]. In the present study, we show that CaM has completely opposite effects on K-Ras-mediated Raf-1 activation. The differential contribution of CaM in the regulat...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Moretó J,Vidal-Quadras M,Pol A,Santos E,Grewal T,Enrich C,Tebar F

    更新日期:2009-12-01 00:00:00

  • CK1δ restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1α/ARNT complex formation.

    abstract::Proliferation of cells under hypoxia is facilitated by metabolic adaptation, mediated by the transcriptional activator Hypoxia Inducible Factor-1 (HIF-1). HIF-1α, the inducible subunit of HIF-1 is regulated by oxygen as well as by oxygen-independent mechanisms involving phosphorylation. We have previously shown that C...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Kourti M,Ikonomou G,Giakoumakis NN,Rapsomaniki MA,Landegren U,Siniossoglou S,Lygerou Z,Simos G,Mylonis I

    更新日期:2015-06-01 00:00:00

  • Individual C1 domains of PKD3 in phorbol ester-induced plasma membrane translocation of PKD3 in intact cells.

    abstract::Protein kinase D3 is a novel member of the serine/threonine kinase family PKD. The regulatory region of PKD contains a tandem repeat of C1 domains designated C1a and C1b that bind diacylglycerol and phorbol esters, and are important membrane targeting modules. Here, we investigate the activities of individual C1 domai...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Anderson G,Chen J,Wang QJ

    更新日期:2005-11-01 00:00:00

  • The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration.

    abstract::Disruption of autophagy plays an import role in neurodegenerative disorders, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates a...

    journal_title:Cellular signalling

    pub_type: 杂志文章,评审


    authors: Heras-Sandoval D,Pérez-Rojas JM,Hernández-Damián J,Pedraza-Chaverri J

    更新日期:2014-12-01 00:00:00

  • Activation of MAP kinases in growth responsive pancreatic cancer cells.

    abstract::The implication of MAP kinases in the proliferation control of pancreatic cancer cells is still unknown. This study was undertaken to examine the contribution of the p44/p42 and p38 MAP kinases in the mitogenic response to epidermal growth factor (EGF) and bombesin in human pancreatic cancer cells, MIA PaCa-2 and PANC...

    journal_title:Cellular signalling

    pub_type: 杂志文章


    authors: Douziech N,Calvo E,Lainé J,Morisset J

    更新日期:1999-08-01 00:00:00