XB130/Tks5 scaffold protein interaction regulates Src-mediated cell proliferation and survival.

Abstract:

:The scaffold protein XB130 regulates cell growth, survival, and migration. Yeast two-hybrid screening suggests that XB130 interacts with another scaffold protein, Tks5. We hypothesized that XB130 and Tks5 form a macromolecular complex to mediate signal transduction cascades for the regulation of cell growth and survival. Coimmunoprecipitation demonstrated that XB130 and Tks5 interact endogenously and form a complex with Src tyrosine kinase. Structure-function studies showed that the fifth SH3 domain of Tks5 binds to the N-terminus of XB130, which contains polyproline-rich motifs. Cell growth and survival studies revealed that down-regulation of XB130 and/or Tks5 reduced cell proliferation, resulting in cell cycle inhibition at the G1 phase and increased caspase 3 activity and apoptosis. Moreover, cell proliferation and survival were increased by overexpression of XB130 or Tks5 but decreased when XB130/Tks5 binding was disrupted by overexpression of XB130 N-terminal deleted mutant and/or Tks5 fifth SH3 domain W1108A mutant. Furthermore, down-regulation of XB130 and/or Tks5 inhibited serum- and growth factor-induced Src activation and downstream phosphorylation of PI3K and Akt. Our results suggest that Tks5, similar to XB130, plays a role in cell proliferation and cell survival and that the interaction between XB130 and Tks5 appears to be critical for regulation of Src-mediated cellular homeostasis.

journal_name

Mol Biol Cell

authors

Moodley S,Hui Bai X,Kapus A,Yang B,Liu M

doi

10.1091/mbc.E15-07-0483

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

4492-502

issue

24

eissn

1059-1524

issn

1939-4586

pii

mbc.E15-07-0483

journal_volume

26

pub_type

杂志文章
  • Role for actin filament turnover and a myosin II motor in cytoskeleton-driven disassembly of the epithelial apical junctional complex.

    abstract::Disassembly of the epithelial apical junctional complex (AJC), composed of the tight junction (TJ) and adherens junction (AJ), is important for normal tissue remodeling and pathogen-induced disruption of epithelial barriers. Using a calcium depletion model in T84 epithelial cells, we previously found that disassembly ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-02-0163

    authors: Ivanov AI,McCall IC,Parkos CA,Nusrat A

    更新日期:2004-06-01 00:00:00

  • The tomosyn homologue, Sro7, is a direct effector of the Rab GTPase, Sec4, in post-Golgi vesicle tethering.

    abstract::The tomosyn/Sro7 family is thought to play an important role in cell surface trafficking both as an effector of Rab family GTPases and as a regulator of plasma-membrane SNARE function. Recent work has determined the binding site of GTP-bound Sec4 on Sro7. Here we examine the effect of mutations in Sro7 that block Sec4...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-02-0138

    authors: Rossi G,Watson K,Kennedy W,Brennwald P

    更新日期:2018-06-15 00:00:00

  • Overlapping roles of Drosophila Drak and Rok kinases in epithelial tissue morphogenesis.

    abstract::Dynamic regulation of cytoskeletal contractility through phosphorylation of the nonmuscle Myosin-II regulatory light chain (MRLC) provides an essential source of tension for shaping epithelial tissues. Rho GTPase and its effector kinase ROCK have been implicated in regulating MRLC phosphorylation in vivo, but evidence...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-04-0328

    authors: Neubueser D,Hipfner DR

    更新日期:2010-08-15 00:00:00

  • c-Jun N-terminal kinase-mediated Rad18 phosphorylation facilitates Polη recruitment to stalled replication forks.

    abstract::The E3 ubiquitin ligase Rad18 chaperones DNA polymerase η (Polη) to sites of UV-induced DNA damage and monoubiquitinates proliferating cell nuclear antigen (PCNA), facilitating engagement of Polη with stalled replication forks and promoting translesion synthesis (TLS). It is unclear how Rad18 activities are coordinate...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-10-0829

    authors: Barkley LR,Palle K,Durando M,Day TA,Gurkar A,Kakusho N,Li J,Masai H,Vaziri C

    更新日期:2012-05-01 00:00:00

  • JunD represses transcription and translation of the tight junction protein zona occludens-1 modulating intestinal epithelial barrier function.

    abstract::The AP-1 transcription factor JunD is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction (TJ) protein zonula occludens (ZO)-1 links the intracellular domain of TJ-transmembrane proteins occludin, claudins...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-02-0175

    authors: Chen J,Xiao L,Rao JN,Zou T,Liu L,Bellavance E,Gorospe M,Wang JY

    更新日期:2008-09-01 00:00:00

  • Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation.

    abstract::The organization of the endoplasmic reticulum (ER) in the cortex of Xenopus oocytes was investigated during maturation and activation using a green fluorescent protein chimera, immunofluorescence, and electron microscopy. Dense clusters of ER developed on the vegetal side (the side opposite the meiotic spindle) during...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.4.1103

    authors: Terasaki M,Runft LL,Hand AR

    更新日期:2001-04-01 00:00:00

  • Posttranslational regulation of the scaffold for Fe-S cluster biogenesis, Isu.

    abstract::Isu, the scaffold protein on which Fe-S clusters are built in the mitochondrial matrix, plays a central role in the biogenesis of Fe-S cluster proteins. We report that the reduction in the activity of several components of the cluster biogenesis system, including the specialized Hsp70 Ssq1, causes a 15-20-fold up-regu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-06-0622

    authors: Andrew AJ,Song JY,Schilke B,Craig EA

    更新日期:2008-12-01 00:00:00

  • A novel family of dehydrin-like proteins is involved in stress response in the human fungal pathogen Aspergillus fumigatus.

    abstract::During a search for genes controlling conidial dormancy in Aspergillus fumigatus, two dehydrin-like genes, DprA and DprB, were identified. The deduced proteins had repeated stretches of 23 amino acids that contained a conserved dehydrin-like protein (DPR) motif. Disrupted DprAΔ mutants were hypersensitive to oxidative...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-11-0914

    authors: Wong Sak Hoi J,Lamarre C,Beau R,Meneau I,Berepiki A,Barre A,Mellado E,Read ND,Latgé JP

    更新日期:2011-06-01 00:00:00

  • Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis.

    abstract::Polo-like kinase 1 (Plk1) is a key regulator of mitotic progression and cell division in eukaryotes. It is highly expressed in tumor cells and considered a potential target for cancer therapy. Here, we report the discovery and application of a novel potent small-molecule inhibitor of mammalian Plk1, ZK-Thiazolidinone ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-05-0517

    authors: Santamaria A,Neef R,Eberspächer U,Eis K,Husemann M,Mumberg D,Prechtl S,Schulze V,Siemeister G,Wortmann L,Barr FA,Nigg EA

    更新日期:2007-10-01 00:00:00

  • Maloriented bivalents have metaphase positions at the spindle equator with more kinetochore microtubules to one pole than to the other.

    abstract::To test the "traction fiber" model for metaphase positioning of bivalents during meiosis, kinetochore fibers of maloriented bivalents, induced during recovery from cold arrest, were analyzed with a liquid crystal polarizing microscope. The measured birefringence retardation of kinetochore fibers is proportional to the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-06-0524

    authors: LaFountain JR Jr,Oldenbourg R

    更新日期:2004-12-01 00:00:00

  • C-terminus of the P4-ATPase ATP8A2 functions in protein folding and regulation of phospholipid flippase activity.

    abstract::ATP8A2 is a P4-ATPase that flips phosphatidylserine and phosphatidylethanolamine across cell membranes. This generates membrane phospholipid asymmetry, a property important in many cellular processes, including vesicle trafficking. ATP8A2 deficiency causes severe neurodegenerative diseases. We investigated the role of...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0453

    authors: Chalat M,Moleschi K,Molday RS

    更新日期:2017-02-01 00:00:00

  • Cdc42 negatively regulates endocytosis during apical membrane maintenance in live animals.

    abstract::Lumen establishment and maintenance are fundamental for tubular organs physiological functions. Most of the studies investigating the mechanisms regulating this process have been carried out in cell cultures or in smaller organisms, whereas little has been done in mammalian model systems in vivo. Here we used the sali...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-10-0615

    authors: Shitara A,Malec L,Ebrahim S,Chen D,Bleck C,Hoffman MP,Weigert R

    更新日期:2019-02-01 00:00:00

  • p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-terminal acetylation.

    abstract::The tumor suppressor protein p53 mediates stress-induced growth arrest or apoptosis and plays a major role in safeguarding genome integrity. In response to DNA damage, p53 can be modified at multiple sites by phosphorylation and acetylation. We report on the characterization of p53 C-terminal phosphorylation by CHK1 a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-08-0689

    authors: Ou YH,Chung PH,Sun TP,Shieh SY

    更新日期:2005-04-01 00:00:00

  • A balance of deubiquitinating enzymes controls cell cycle entry.

    abstract::Protein degradation during the cell cycle is controlled by the opposing activities of ubiquitin ligases and deubiquitinating enzymes (DUBs). Although the functions of ubiquitin ligases in the cell cycle have been studied extensively, the roles of DUBs in this process are less well understood. Here, we used an overexpr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-07-0425

    authors: Mapa CE,Arsenault HE,Conti MM,Poti KE,Benanti JA

    更新日期:2018-11-15 00:00:00

  • Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.

    abstract::The cdc25 tyrosine phosphatase is known to activate cdc2 kinase in the G2/M transition by dephosphorylation of tyrosine 15. To determine how entry into M-phase in eukaryotic cells is controlled, we have investigated the regulation of the cdc25 protein in Xenopus eggs and oocytes. Two closely related Xenopus cdc25 gene...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.8.927

    authors: Izumi T,Walker DH,Maller JL

    更新日期:1992-08-01 00:00:00

  • The role of the tethering proteins p115 and GM130 in transport through the Golgi apparatus in vivo.

    abstract::Biochemical data have shown that COPI-coated vesicles are tethered to Golgi membranes by a complex of at least three proteins: p115, giantin, and GM130. p115 binds to giantin on the vesicles and to GM130 on the membrane. We now examine the function of this tethering complex in vivo. Microinjection of an N-terminal pep...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.2.635

    authors: Seemann J,Jokitalo EJ,Warren G

    更新日期:2000-02-01 00:00:00

  • Alpha5beta1 integrin controls cyclin D1 expression by sustaining mitogen-activated protein kinase activity in growth factor-treated cells.

    abstract::Cyclin D1 expression is jointly regulated by growth factors and cell adhesion to the extracellular matrix in many cell types. Growth factors are thought to regulate cyclin D1 expression because they stimulate sustained extracellular signal-regulated kinase (ERK) activity. However, we show here that growth factors indu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.10.3197

    authors: Roovers K,Davey G,Zhu X,Bottazzi ME,Assoian RK

    更新日期:1999-10-01 00:00:00

  • RSBP-1 is a membrane-targeting subunit required by the Galpha(q)-specific but not the Galpha(o)-specific R7 regulator of G protein signaling in Caenorhabditis elegans.

    abstract::Regulator of G protein signaling (RGS) proteins inhibit G protein signaling by activating Galpha GTPase activity, but the mechanisms that regulate RGS activity are not well understood. The mammalian R7 binding protein (R7BP) can interact with all members of the R7 family of RGS proteins, and palmitoylation of R7BP can...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-07-0642

    authors: Porter MY,Koelle MR

    更新日期:2010-01-15 00:00:00

  • Many roads to symmetry breaking: molecular mechanisms and theoretical models of yeast cell polarity.

    abstract::Mathematical modeling has been instrumental in identifying common principles of cell polarity across diverse systems. These principles include positive feedback loops that are required to destabilize a spatially uniform state of the cell. The conserved small G-protein Cdc42 is a master regulator of eukaryotic cellular...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章,评审

    doi:10.1091/mbc.E16-10-0739

    authors: Goryachev AB,Leda M

    更新日期:2017-02-01 00:00:00

  • NGF controls dendrite development in hippocampal neurons by binding to p75NTR and modulating the cellular targets of Notch.

    abstract::Notch and neurotrophins control neuronal shape, but it is not known whether their signaling pathways intersect. Here we report results from hippocampal neuronal cultures that are in support of this possibility. We found that low cell density or blockade of Notch signaling by a soluble Delta-Fc ligand decreased the mRN...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-05-0438

    authors: Salama-Cohen P,Arévalo MA,Meier J,Grantyn R,Rodríguez-Tébar A

    更新日期:2005-01-01 00:00:00

  • ATP-dependent membrane assembly of F-actin facilitates membrane fusion.

    abstract::We recently established an in vitro assay that monitors the fusion between latex-bead phagosomes and endocytic organelles in the presence of J774 macrophage cytosol (). Here, we show that different reagents affecting the actin cytoskeleton can either inhibit or stimulate this fusion process. Because the membranes of p...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.1.155

    authors: Jahraus A,Egeberg M,Hinner B,Habermann A,Sackman E,Pralle A,Faulstich H,Rybin V,Defacque H,Griffiths G

    更新日期:2001-01-01 00:00:00

  • Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.

    abstract::Alzheimer's β-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we fi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-06-1111

    authors: Chiba K,Araseki M,Nozawa K,Furukori K,Araki Y,Matsushima T,Nakaya T,Hata S,Saito Y,Uchida S,Okada Y,Nairn AC,Davis RJ,Yamamoto T,Kinjo M,Taru H,Suzuki T

    更新日期:2014-11-05 00:00:00

  • Essential role of phosphorylation of MCM2 by Cdc7/Dbf4 in the initiation of DNA replication in mammalian cells.

    abstract::We report the identification of Cdc7/Dbf4 phosphorylation sites in human MCM2 and the determination of the role of Cdc7/Dbf4 phosphorylation of MCM2 in the initiation of DNA replication. Using immunoblotting, immunofluorescence, and high-speed automated cell-imaging analyses with antibodies specific against MCM2 and C...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-03-0241

    authors: Tsuji T,Ficarro SB,Jiang W

    更新日期:2006-10-01 00:00:00

  • Oxidative folding and assembly with transthyretin are sequential events in the biogenesis of retinol binding protein in the endoplasmic reticulum.

    abstract::Retinol-binding protein (RBP) is secreted out of the cell in its ligand-bound holo-form. The apo-form of RBP is selectively retained within the endoplasmic reticulum (ER) by a mechanism that remains unknown. Using isolated microsomal system, we have recapitulated the biogenesis of RBP involving its oxidative folding a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-01-0026

    authors: Selvaraj SR,Bhatia V,Tatu U

    更新日期:2008-12-01 00:00:00

  • Morphogenesis in Kyoto: a confluence of cell and developmental biology.

    abstract::Understanding morphogenesis is the ultimate multidisciplinary (ad)venture. Three-dimensional tissues are generated from the actions of genes, biochemical pathways, and cells that form multicellular networks and interact with their biomechanical environment. A comprehensive explanation of morphogenetic processes must e...

    journal_title:Molecular biology of the cell

    pub_type:

    doi:10.1091/mbc.e09-12-1076

    authors: Zallen JA,Yap AS

    更新日期:2010-03-15 00:00:00

  • Onward from the cradle.

    abstract::This essay records a voyage of discovery from the "cradle of cell biology" to the present, focused on the biology of the oldest known cell organelle, the cilium. In the "romper room" of cilia and microtubule (MT) biology, the sliding MT hypothesis of ciliary motility was born. From the "summer of love," students and c...

    journal_title:Molecular biology of the cell

    pub_type: 历史文章,杂志文章

    doi:10.1091/mbc.E14-05-1014

    authors: Satir P

    更新日期:2014-11-01 00:00:00

  • Tenascin-C modulates matrix contraction via focal adhesion kinase- and Rho-mediated signaling pathways.

    abstract::A provisional matrix consisting of fibrin and fibronectin (FN) is deposited at sites of tissue damage and repair. This matrix serves as a scaffold for fibroblast migration into the wound where these cells deposit new matrix to replace lost or damaged tissue and eventually contract the matrix to bring the margins of th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-05-0292

    authors: Midwood KS,Schwarzbauer JE

    更新日期:2002-10-01 00:00:00

  • Separate roles of IQGAP Rng2p in forming and constricting the Schizosaccharomyces pombe cytokinetic contractile ring.

    abstract::Eukaryotic cells require IQGAP family multidomain adapter proteins for cytokinesis, but many questions remain about how IQGAPs contribute to the process. Here we show that fission yeast IQGAP Rng2p is required for both the normal process of contractile ring formation from precursor nodes and an alternative mechanism b...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-10-0775

    authors: Tebbs IR,Pollard TD

    更新日期:2013-06-01 00:00:00

  • Temporal regulation of cell polarity via the interaction of the Ras GTPase Rsr1 and the scaffold protein Bem1.

    abstract::The Cdc42 guanosine triphosphatase (GTPase) plays a central role in polarity development in species ranging from yeast to humans. In budding yeast, a specific growth site is selected in the G1 phase. Rsr1, a Ras GTPase, interacts with Cdc42 and its associated proteins to promote polarized growth at the proper bud site...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-02-0106

    authors: Miller KE,Lo WC,Chou CS,Park HO

    更新日期:2019-09-15 00:00:00

  • A prefoldin-associated WD-repeat protein (WDR92) is required for the correct architectural assembly of motile cilia.

    abstract::WDR92 is a highly conserved WD-repeat protein that has been proposed to be involved in apoptosis and also to be part of a prefoldin-like cochaperone complex. We found that WDR92 has a phylogenetic signature that is generally compatible with it playing a role in the assembly or function of specifically motile cilia. To...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-01-0040

    authors: Patel-King RS,King SM

    更新日期:2016-04-15 00:00:00