Tyrosine phosphorylation of the Gα-interacting protein GIV promotes activation of phosphoinositide 3-kinase during cell migration.

Abstract:

:GIV (Gα-interacting vesicle-associated protein; also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine phosphoprotein that directly binds to and activates phosphoinositide 3-kinase (PI3K). Upon ligand stimulation of various receptors, GIV was phosphorylated at tyrosine-1764 and tyrosine-1798 by both receptor and non-receptor tyrosine kinases. These phosphorylation events enabled direct binding of GIV to the amino- and carboxyl-terminal Src homology 2 domains of p85α, a regulatory subunit of PI3K; stabilized receptor association with PI3K; and enhanced PI3K activity at the plasma membrane to trigger cell migration. Tyrosine phosphorylation of GIV and its association with p85α increased during metastatic progression of a breast carcinoma. These results suggest a mechanism by which multiple receptors activate PI3K through tyrosine phosphorylation of GIV, thereby making the GIV-PI3K interaction a potential therapeutic target within the PI3K-Akt pathway.

journal_name

Sci Signal

journal_title

Science signaling

authors

Lin C,Ear J,Pavlova Y,Mittal Y,Kufareva I,Ghassemian M,Abagyan R,Garcia-Marcos M,Ghosh P

doi

10.1126/scisignal.2002049

subject

Has Abstract

pub_date

2011-09-27 00:00:00

pages

ra64

issue

192

eissn

1945-0877

issn

1937-9145

pii

4/192/ra64

journal_volume

4

pub_type

杂志文章
  • Inositol pyrophosphates as mammalian cell signals.

    abstract::Inositol pyrophosphates are highly energetic inositol polyphosphate molecules present in organisms from slime molds and yeast to mammals. Distinct classes of enzymes generate different forms of inositol pyrophosphates. The biosynthesis of these substances principally involves phosphorylation of inositol hexakisphospha...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.2001958

    authors: Chakraborty A,Kim S,Snyder SH

    更新日期:2011-08-23 00:00:00

  • Evolution of human, chicken, alligator, frog, and zebrafish mineralocorticoid receptors: Allosteric influence on steroid specificity.

    abstract::Although multiple steroid ligands of the glucocorticoid, mineralocorticoid, and progestin families bind to and regulate the activity of mineralocorticoid receptors (MRs), the responses to these ligands differ across species. To understand how the different domains of MRs contribute to the ligand-induced activation or ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aao1520

    authors: Katsu Y,Oka K,Baker ME

    更新日期:2018-07-03 00:00:00

  • Degrons in cancer.

    abstract::Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aak9982

    authors: Mészáros B,Kumar M,Gibson TJ,Uyar B,Dosztányi Z

    更新日期:2017-03-14 00:00:00

  • The early synthesis of p35 and activation of CDK5 in LPS-stimulated macrophages suppresses interleukin-10 production.

    abstract::Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimu...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aab3156

    authors: Na YR,Jung D,Gu GJ,Jang AR,Suh YH,Seok SH

    更新日期:2015-11-24 00:00:00

  • Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels.

    abstract::Activation of Ca2+-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca2+ signals (Ca2+ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf6625

    authors: Khavandi K,Baylie RA,Sugden SA,Ahmed M,Csato V,Eaton P,Hill-Eubanks DC,Bonev AD,Nelson MT,Greenstein AS

    更新日期:2016-10-11 00:00:00

  • 4E-BP2 hardwires lymphocytes for rapamycin sensitivity.

    abstract::The mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] inhibitor rapamycin is a potent inhibitor of T and B lymphocyte growth and proliferation. In this issue of Science Signaling, So et al found that the isoform of 4E-BP (4E-BP2) in lymphocytes that regulates messenger RNA translation is more sensitive...

    journal_title:Science signaling

    pub_type: 评论,杂志文章,评审

    doi:10.1126/scisignal.aaf8190

    authors: Abraham RT

    更新日期:2016-05-31 00:00:00

  • Increased MKK4 abundance with replicative senescence is linked to the joint reduction of multiple microRNAs.

    abstract::MKK4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator of c-Jun N-terminal kinase and p38. Here, we report that the abundance of MKK4 increases in senescent human diploid fibroblasts through enhanced translation. We identified four microRNAs (miR-15b, miR-24, miR-25, and miR-141) that target ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000442

    authors: Marasa BS,Srikantan S,Masuda K,Abdelmohsen K,Kuwano Y,Yang X,Martindale JL,Rinker-Schaeffer CW,Gorospe M

    更新日期:2009-10-27 00:00:00

  • Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis.

    abstract::Like phosphorylation, the addition of O-linked beta-N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous, reversible process that modifies serine and threonine residues on nuclear and cytoplasmic proteins. Overexpression of the enzyme that adds O-GlcNAc to target proteins, O-GlcNAc transferase (OGT), perturbs cytokin...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000526

    authors: Wang Z,Udeshi ND,Slawson C,Compton PD,Sakabe K,Cheung WD,Shabanowitz J,Hunt DF,Hart GW

    更新日期:2010-01-12 00:00:00

  • The Src family kinase Fgr is a transforming oncoprotein that functions independently of SH3-SH2 domain regulation.

    abstract::Fgr is a member of the Src family of nonreceptor tyrosine kinases, which are overexpressed and constitutively active in many human cancers. Fgr expression is restricted to myeloid hematopoietic cells and is markedly increased in a subset of bone marrow samples from patients with acute myeloid leukemia (AML). Here, we ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aat5916

    authors: Shen K,Moroco JA,Patel RK,Shi H,Engen JR,Dorman HR,Smithgall TE

    更新日期:2018-10-23 00:00:00

  • The GAS6-AXL signaling network is a mesenchymal (Mes) molecular subtype-specific therapeutic target for ovarian cancer.

    abstract::Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal ("Mes") subtype have a poorer prognosis than patients with tumors of an epithelial ("Epi") subtype. We evaluated GEMS of ovarian cancer patients for molecul...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf8175

    authors: Antony J,Tan TZ,Kelly Z,Low J,Choolani M,Recchi C,Gabra H,Thiery JP,Huang RY

    更新日期:2016-10-04 00:00:00

  • Controlling long-term signaling: receptor dynamics determine attenuation and refractory behavior of the TGF-β pathway.

    abstract::Understanding the complex dynamics of growth factor signaling requires both mechanistic and kinetic information. Although signaling dynamics have been studied for pathways downstream of receptor tyrosine kinases and G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors, they have not been inv...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2004416

    authors: Vizán P,Miller DS,Gori I,Das D,Schmierer B,Hill CS

    更新日期:2013-12-10 00:00:00

  • The chemokine CXCL12 generates costimulatory signals in T cells to enhance phosphorylation and clustering of the adaptor protein SLP-76.

    abstract::The CXC chemokine CXCL12 mediates the chemoattraction of T cells and enhances the stimulation of T cells through the T cell receptor (TCR). The adaptor SLP-76 [Src homology 2 (SH2) domain-containing leukocyte protein of 76 kD] has two key tyrosine residues, Tyr(113) and Tyr(128), that mediate signaling downstream of t...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2004018

    authors: Smith X,Schneider H,Köhler K,Liu H,Lu Y,Rudd CE

    更新日期:2013-07-30 00:00:00

  • The effects of acute and chronic stress on diabetes control.

    abstract::Stress is an important contributor to pathological conditions in humans. Hormonal changes that occur during acute and chronic stress situations can affect glucose homeostasis in both healthy people and in those with diabetes. Several studies have reported a negative effect of acute stress on maintenance of blood gluco...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.2003508

    authors: Marcovecchio ML,Chiarelli F

    更新日期:2012-10-23 00:00:00

  • The glycosylation pathway is required for the secretion of Slit and for the maintenance of the Slit receptor Robo on axons.

    abstract::Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aam5841

    authors: Manavalan MA,Jayasinghe VR,Grewal R,Bhat KM

    更新日期:2017-06-20 00:00:00

  • The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4+ T cells.

    abstract::The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were ident...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aar3083

    authors: Gaud G,Roncagalli R,Chaoui K,Bernard I,Familiades J,Colacios C,Kassem S,Monsarrat B,Burlet-Schiltz O,de Peredo AG,Malissen B,Saoudi A

    更新日期:2018-07-10 00:00:00

  • Autophagy and vitamin D.

    abstract::Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression. ...

    journal_title:Science signaling

    pub_type: 评论,杂志文章

    doi:10.1126/scisignal.aan2526

    authors: Mushegian AA

    更新日期:2017-03-21 00:00:00

  • miR-221/222 targeting of trichorhinophalangeal 1 (TRPS1) promotes epithelial-to-mesenchymal transition in breast cancer.

    abstract::Compared with the luminal subtype, the basal-like subtype of breast cancer has an aggressive clinical behavior, but the reasons for this difference between the two subtypes are poorly understood. We identified microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as basal-like subtype-specific miRNAs that decrease expr...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002258

    authors: Stinson S,Lackner MR,Adai AT,Yu N,Kim HJ,O'Brien C,Spoerke J,Jhunjhunwala S,Boyd Z,Januario T,Newman RJ,Yue P,Bourgon R,Modrusan Z,Stern HM,Warming S,de Sauvage FJ,Amler L,Yeh RF,Dornan D

    更新日期:2011-08-09 00:00:00

  • Attenuation of rabies virulence: takeover by the cytoplasmic domain of its envelope protein.

    abstract::The capacity of a rabies virus to promote neuronal survival (a signature of virulence) or death (a marker of attenuation) depends on the cellular partners recruited by the PDZ-binding site (PDZ-BS) of its envelope glycoprotein (G). Neuronal survival requires the selective association of the PDZ-BS of G with the PDZ do...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000510

    authors: Préhaud C,Wolff N,Terrien E,Lafage M,Mégret F,Babault N,Cordier F,Tan GS,Maitrepierre E,Ménager P,Chopy D,Hoos S,England P,Delepierre M,Schnell MJ,Buc H,Lafon M

    更新日期:2010-01-19 00:00:00

  • Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple.

    abstract::Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor ty...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aao4220

    authors: Aznar N,Ear J,Dunkel Y,Sun N,Satterfield K,He F,Kalogriopoulos NA,Lopez-Sanchez I,Ghassemian M,Sahoo D,Kufareva I,Ghosh P

    更新日期:2018-02-27 00:00:00

  • Real-time dynamics of peptide ligand-dependent receptor complex formation in planta.

    abstract::The CLAVATA (CLV) and flagellin (flg) signaling pathways act through peptide ligands and closely related plasma membrane-localized receptor-like kinases (RLKs). The plant peptide CLV3 regulates stem cell homeostasis, whereas the bacterial flg22 peptide elicits defense responses. We applied multiparameter fluorescence ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aab0598

    authors: Somssich M,Ma Q,Weidtkamp-Peters S,Stahl Y,Felekyan S,Bleckmann A,Seidel CA,Simon R

    更新日期:2015-08-04 00:00:00

  • Full focus on calcium.

    abstract::Intracellular calcium (Ca2+) signals are of prime importance for cellular function and behavior and are underpinned by a plethora of Ca2+ channels, pumps, transporters, and binding proteins that are regulated in complex ways. A series of biennial meetings, the International Meetings of the European Calcium Society (EC...

    journal_title:Science signaling

    pub_type:

    doi:10.1126/scisignal.aaz0961

    authors: Parys JB,Guse AH

    更新日期:2019-09-17 00:00:00

  • Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling.

    abstract::The interplay between calcium ion (Ca(2+)) and cyclic adenosine monophosphate (cAMP) signaling underlies crucial aspects of cell homeostasis. The membrane-bound Ca(2+)-regulated adenylyl cyclases (ACs) are pivotal points of this integration. These enzymes display high selectivity for Ca(2+) entry arising from the acti...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002299

    authors: Willoughby D,Everett KL,Halls ML,Pacheco J,Skroblin P,Vaca L,Klussmann E,Cooper DM

    更新日期:2012-04-10 00:00:00

  • Arabidopsis ATXR2 deposits H3K36me3 at the promoters of LBD genes to facilitate cellular dedifferentiation.

    abstract::Cellular dedifferentiation, the transition of differentiated somatic cells to pluripotent stem cells, ensures developmental plasticity and contributes to wound healing in plants. Wounding induces cells to form a mass of unorganized pluripotent cells called callus at the wound site. Explanted cells can also form callus...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aan0316

    authors: Lee K,Park OS,Seo PJ

    更新日期:2017-11-28 00:00:00

  • Noncanonical NF-κB signaling is limited by classical NF-κB activity.

    abstract::Precise regulation of nuclear factor κB (NF-κB) signaling is crucial for normal immune responses, and defective NF-κB activity underlies a range of immunodeficiencies. NF-κB is activated through two signaling cascades: the classical and noncanonical pathways. The classical pathway requires inhibitor of κB kinase β (IK...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2004557

    authors: Gray CM,Remouchamps C,McCorkell KA,Solt LA,Dejardin E,Orange JS,May MJ

    更新日期:2014-02-04 00:00:00

  • ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases.

    abstract::ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and prote...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aac4374

    authors: Kline CL,Van den Heuvel AP,Allen JE,Prabhu VV,Dicker DT,El-Deiry WS

    更新日期:2016-02-16 00:00:00

  • SMAC mimetics and RIPK inhibitors as therapeutics for chronic inflammatory diseases.

    abstract::New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin liga...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aax8295

    authors: Jensen S,Seidelin JB,LaCasse EC,Nielsen OH

    更新日期:2020-02-18 00:00:00

  • Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner.

    abstract::The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.abd2494

    authors: Abd-Elrahman KS,Albaker A,de Souza JM,Ribeiro FM,Schlossmacher MG,Tiberi M,Hamilton A,Ferguson SSG

    更新日期:2020-12-15 00:00:00

  • Controlling the number of tooth rows.

    abstract::The organization and renewal capacity of teeth vary greatly among vertebrates. Mammals have only one row of teeth that are renewed at most once, whereas many nonmammalian species have multirowed dentitions and show remarkable capacity to replace their teeth throughout life. Although knowledge on the genetic basis of t...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.285pe53

    authors: Mikkola ML

    更新日期:2009-08-25 00:00:00

  • The extracellular calcium-sensing receptor (CaSR) is a critical modulator of skeletal development.

    abstract::The extracellular Ca(2+)-sensing receptor (CaSR) plays a nonredundant role in the functions of the parathyroid gland (PTG) and the kidney. Severe hyperparathyroidism, premature death, and incomplete gene excision in Casr(-/-) mice have precluded the assessment of CaSR function in other tissues. We generated mice with ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.1159945

    authors: Chang W,Tu C,Chen TH,Bikle D,Shoback D

    更新日期:2008-09-02 00:00:00

  • Emerging from the shade of p53 mutants: N-terminally truncated variants of the p53 family in EMT signaling and cancer progression.

    abstract::The prevailing view has been that N-terminally truncated p53 family isoforms (ΔNp53, ΔNp63, and DNp73) predominantly counteract cell cycle arrest and apoptosis. Recent progress in the field extend these well-known functions and place these isoforms in the center of a comprehensive regulatory network controlling major ...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.2005699

    authors: Engelmann D,Pützer BM

    更新日期:2014-09-30 00:00:00