Intramolecular interaction between phosphorylated tyrosine-783 and the C-terminal Src homology 2 domain activates phospholipase C-gamma1.

Abstract:

:Phospholipase C-gamma1 (PLC-gamma1) contains two tandem Src homology 2 (SH2) domains. The NH(2)-terminal SH2 domain has been known to mediate the binding of PLC-gamma1 to receptor protein tyrosine kinases, which then activate PLC-gamma1 via phosphorylation at Y783. We now show that the phosphorylated Y783 residue (pY783) associates with the COOH-terminal SH2 domain [SH2(C)] within the same molecule of PLC-gamma1. The specificity of this intramolecular interaction is demonstrated in several ways. The mutation of SH2(C), but not of the NH(2)-terminal SH2 domain, exposes pY783 and makes it available for binding by anti-pY783 antibodies, for intermolecular association with a GST fusion protein containing the tandem SH2 domains of PLC-gamma1 and for dephosphorylation by phosphatases. The intramolecular interaction between pY783 and SH2(C) induces a rearrangement of surface charge such that PLC-gamma1 molecules phosphorylated at Y783 are retained more strongly by heparin resins than are unphosphorylated molecules. Finally, the intramolecular interaction of pY783 with SH2(C) results in activation of phospholipase activity. Our results thus clarify the molecular mechanism of PLC-gamma1 activation, revealing the specific function of pY783 and the distinct roles of the two SH2 domains in this process.

authors

Poulin B,Sekiya F,Rhee SG

doi

10.1073/pnas.0409590102

keywords:

subject

Has Abstract

pub_date

2005-03-22 00:00:00

pages

4276-81

issue

12

eissn

0027-8424

issn

1091-6490

pii

0409590102

journal_volume

102

pub_type

杂志文章
  • The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells.

    abstract::RNA helicases play roles in various essential biological processes such as RNA splicing and editing. Recent in vitro studies show that RNA helicases are involved in immune responses toward viruses, serving as viral RNA sensors or immune signaling adaptors. However, there is still a lack of in vivo data to support the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2017432118

    authors: Wang Y,He K,Sheng B,Lei X,Tao W,Zhu X,Wei Z,Fu R,Wang A,Bai S,Zhang Z,Hong N,Ye C,Tian Y,Wang J,Li M,Zhang K,Li L,Yang H,Li HB,Flavell RA,Zhu S

    更新日期:2021-01-26 00:00:00

  • Stabilization of electron spin resonance probes for photosynthesis studies.

    abstract::The major obstacle to the study of functional/structural interrelationships of spinach chloroplasts by using spin labels has been the rapid loss of the electron paramagnetic resonance (EPR) signals upon illumination with visible light. The present study demonstrates that the addition of ferredoxin and NADP+ in the pre...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.8.3107

    authors: Sun AS,Calvin M

    更新日期:1975-08-01 00:00:00

  • Exploring the proton pump and exit pathway for pumped protons in cytochrome ba3 from Thermus thermophilus.

    abstract::The heme-copper oxygen reductases are redox-driven proton pumps. In the current work, the effects of mutations in a proposed exit pathway for pumped protons are examined in the ba(3)-type oxygen reductase from Thermus thermophilus, leading from the propionates of heme a(3) to the interface between subunits I and II. R...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1107345109

    authors: Chang HY,Choi SK,Vakkasoglu AS,Chen Y,Hemp J,Fee JA,Gennis RB

    更新日期:2012-04-03 00:00:00

  • Immunologic evidence that the gene for L-gulono-gamma-lactone oxidase is not expressed in animals subject to scurvy.

    abstract::L-Gulono-gamma-lactone oxidase (L-gulono-gamma-lactone:oxygen 2-oxidoreductase, EC 1.1.3.8) is the enzyme that catalyzes the terminal step of L-ascorbic acid biosynthesis in mammalian liver. The absence of the oxidase activity in primates and guinea pigs is the reason why these animals are subject to scurvy, which mus...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.6.2066

    authors: Nishikimi M,Udenfriend S

    更新日期:1976-06-01 00:00:00

  • Cap-dependent RNA splicing in a HeLa nuclear extract.

    abstract::We have studied the involvement of the 5' cap structure in the splicing of precursor mRNAs in a HeLa nuclear extract. We show that precursor mRNAs are spliced efficiently only when they possess a cap structure and that preincubation of a HeLa nuclear extract rendered the splicing reaction highly sensitive to inhibitio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.22.7590

    authors: Edery I,Sonenberg N

    更新日期:1985-11-01 00:00:00

  • Euler-Poisson equations on Lie algebras and the N-dimensional heavy rigid body.

    abstract::The classical Euler-Poisson equations describing the motion of a heavy rigid body about a fixed point are generalized to arbitrary Lie algebras as Hamiltonian systems on coad-joint orbits of a tangent bundle Lie group. the N-dimensional Lagrange and symmetric heavy top are thereby shown to be completely integrable. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.3.1327

    authors: Ratiu T

    更新日期:1981-03-01 00:00:00

  • The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes.

    abstract::The antimicrobial peptide hepcidin appears to play a central role in the regulation of iron homeostasis. In intact animals, iron overload or the injection of lipopolysaccharide (LPS) stimulates transcription of HAMP, the gene that encodes hepcidin. In isolated hepatocytes, IL-6, an inflammatory cytokine the production...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0403108101

    authors: Lee P,Peng H,Gelbart T,Beutler E

    更新日期:2004-06-22 00:00:00

  • Myosin IC generates power over a range of loads via a new tension-sensing mechanism.

    abstract::Myosin IC (myo1c), a widely expressed motor protein that links the actin cytoskeleton to cell membranes, has been associated with numerous cellular processes, including insulin-stimulated transport of GLUT4, mechanosensation in sensory hair cells, endocytosis, transcription of DNA in the nucleus, exocytosis, and membr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1207811109

    authors: Greenberg MJ,Lin T,Goldman YE,Shuman H,Ostap EM

    更新日期:2012-09-11 00:00:00

  • Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface.

    abstract::The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. Here we show that γδ intraepithelial lymphocytes (γδ IEL) of the small intestine produc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1019574108

    authors: Ismail AS,Severson KM,Vaishnava S,Behrendt CL,Yu X,Benjamin JL,Ruhn KA,Hou B,DeFranco AL,Yarovinsky F,Hooper LV

    更新日期:2011-05-24 00:00:00

  • Sex-dependent expression of mouse testosterone 16 alpha-hydroxylase (cytochrome P-450(16) alpha): cDNA cloning and pretranslational regulation.

    abstract::By using both double-colony hybridization and an in situ immunostaining assay for transformants, 39 cDNA clones (clone p-16 alpha) encoding mouse liver microsomal testosterone 16 alpha-hydroxylase (cytochrome P-450(16) alpha) were isolated from a cDNA library constructed in the cloning vector pUC-9 with poly(A)+ RNA i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.7.2024

    authors: Harada N,Negishi M

    更新日期:1985-04-01 00:00:00

  • Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection.

    abstract::Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1115621109

    authors: Fanning S,Hall LJ,Cronin M,Zomer A,MacSharry J,Goulding D,Motherway MO,Shanahan F,Nally K,Dougan G,van Sinderen D

    更新日期:2012-02-07 00:00:00

  • Ten- to 50-nm-long quasi-ballistic carbon nanotube devices obtained without complex lithography.

    abstract::A simple method combining photolithography and shadow (or angle) evaporation is developed to fabricate single-walled carbon nanotube (SWCNT) devices with tube lengths of approximately 10-50 nm between metal contacts. Large numbers of such short devices are obtained without the need of complex tools such as electron be...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0404450101

    authors: Javey A,Qi P,Wang Q,Dai H

    更新日期:2004-09-14 00:00:00

  • Determination of the minimum polypeptide lengths of the functionally active sites of human interleukins 1 alpha and 1 beta.

    abstract::Interleukin 1 (IL-1) is a two-member family of proteins (IL-1 alpha and IL-1 beta) that mediates a diverse series of immune and inflammatory responses. These two proteins have only 26% amino acid homology yet bind to the same receptor. It is of importance to define the active sites of these molecules in order to under...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.13.4572

    authors: Mosley B,Dower SK,Gillis S,Cosman D

    更新日期:1987-07-01 00:00:00

  • Local sources of retinoic acid coincide with retinoid-mediated transgene activity during embryonic development.

    abstract::We have assessed whether retinoic acid (RA) comes from local sources or is available widely to activate gene expression in embryos. We used an RA-responsive indicator cell line, L-C2A5, to localize RA sources. In these cells, an RA-sensitive promoter/lacZ reporter construct used previously by us to produce indicator t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.14.6572

    authors: Colbert MC,Linney E,LaMantia AS

    更新日期:1993-07-15 00:00:00

  • Expression of three mammalian cDNAs that interfere with RAS function in Saccharomyces cerevisiae.

    abstract::Saccharomyces cerevisiae strains expressing the activated RAS2Val19 gene or lacking both cAMP phosphodiesterase genes, PDE1 and PDE2, have impaired growth control and display an acute sensitivity to heat shock. We have isolated two classes of mammalian cDNAs from yeast expression libraries that suppress the heat shock...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.7.2913

    authors: Colicelli J,Nicolette C,Birchmeier C,Rodgers L,Riggs M,Wigler M

    更新日期:1991-04-01 00:00:00

  • New World tetraploid cottons contain Old World cytoplasm.

    abstract::New World tetraploid cottons (Gossypium spp.) originated through hybridization of ancestral diploid species that presently have allopatric ranges in Asia-Africa (the A genome) and the New World tropics and subtropics (the D genome). Despite intensive study, the identity of the parental diploids and the antiquity of po...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.11.4132

    authors: Wendel JF

    更新日期:1989-06-01 00:00:00

  • Abscisic acid signal transduction in the barley aleurone is mediated by phospholipase D activity.

    abstract::The plant hormones abscisic acid (ABA) and gibberellic acid (GA) are important regulators of the dormancy and germination of seeds. In cereals, GA enhances the synthesis and secretion of enzymes (principally alpha-amylases) in the aleurone cells of the endosperm, which then mobilize the storage reserves that fuel germ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.5.2697

    authors: Ritchie S,Gilroy S

    更新日期:1998-03-03 00:00:00

  • Mitogenic properties of a calcium ionophore, A23187.

    abstract::A23187 is a carboxylic antibiotic that selectively transfers calcium, magnesium, and other divalent cations across biologic membranes. This ionophore was found to produce morphologic blast transformation, DNA synthesis, and mitosis in human lymphocytes. Several hours of ionophore-cell contact were necessary to produce...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.12.5088

    authors: Luckasen JR,White JG,Kersey JH

    更新日期:1974-12-01 00:00:00

  • Hoping for optimality or designing for inclusion: Persistence, learning, and the social network of citizen science.

    abstract::The explosive growth in citizen science combined with a recalcitrance on the part of mainstream science to fully embrace this data collection technique demands a rigorous examination of the factors influencing data quality and project efficacy. Patterns of contributor effort and task performance have been well reviewe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,meta分析

    doi:10.1073/pnas.1807186115

    authors: Parrish JK,Jones T,Burgess HK,He Y,Fortson L,Cavalier D

    更新日期:2019-02-05 00:00:00

  • Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV.

    abstract::Nerve growth factor (NGF) is a neurotrophin with the ability to exert specific effects on cells of the immune system. Human monocytes/macrophages (M/M) infected in vitro with HIV type 1 (HIV-1) are able to produce substantial levels of NGF that are associated with enhanced expression of the high-affinity NGF receptor ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.24.14013

    authors: Garaci E,Caroleo MC,Aloe L,Aquaro S,Piacentini M,Costa N,Amendola A,Micera A,Caliò R,Perno CF,Levi-Montalcini R

    更新日期:1999-11-23 00:00:00

  • Use of a synthetic peptide antigen to generate antisera reactive with a proteolytic processing site in native human proinsulin: demonstration of cleavage within clathrin-coated (pro)secretory vesicles.

    abstract::Polyclonal antibodies reactive with a cleavage site in human proinsulin (HPI) (C-peptide-A-chain junction) have been raised (rabbit, guinea pig) using a synthetic peptide antigen coupled with keyhole limpet hemocyanin. These antisera recognize native HPI and des-31,32-HPI equally well but react 20-50 times less well w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.17.6184

    authors: Steiner DF,Michael J,Houghten R,Mathieu M,Gardner PR,Ravazzola M,Orci L

    更新日期:1987-09-01 00:00:00

  • Communicating the deadly consequences of global warming for human heat stress.

    abstract::In December of 2015, the international community pledged to limit global warming to below 2 °C above preindustrial (PI) to prevent dangerous climate change. However, to what extent, and for whom, is danger avoided if this ambitious target is realized? We address these questions by scrutinizing heat stress, because the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1617526114

    authors: Matthews TK,Wilby RL,Murphy C

    更新日期:2017-04-11 00:00:00

  • Specificity in the activation and control of transcription factor E2F-dependent apoptosis.

    abstract::Previous work has demonstrated a role for the E2F1 gene product in signaling apoptosis, both as a result of the deregulation of the Rb/E2F pathway as well as in response to DNA damage. We now show that the ability of cells to suppress the apoptotic potential of E2F1, as might occur during the course of normal cellular...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1831408100

    authors: Hallstrom TC,Nevins JR

    更新日期:2003-09-16 00:00:00

  • Macronuclear DNA of the hypotrichous ciliate Oxytricha fallax.

    abstract::DNA in the macronuclei of Oxytricha fallax, as in other hypotrichous ciliate protozoa, exists as small, achromosomal molecules rather than in chromosomes. We report studies on O. fallax DNA using physicochemical procedures and nucleic acid hybridization. Macronuclear DNA molecules range in size from 22 kilobase pairs ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.10.4992

    authors: Rae PM,Spear BB

    更新日期:1978-10-01 00:00:00

  • Measuring single-cell density.

    abstract::We have used a microfluidic mass sensor to measure the density of single living cells. By weighing each cell in two fluids of different densities, our technique measures the single-cell mass, volume, and density of approximately 500 cells per hour with a density precision of 0.001 g mL(-1). We observe that the intrins...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1104651108

    authors: Grover WH,Bryan AK,Diez-Silva M,Suresh S,Higgins JM,Manalis SR

    更新日期:2011-07-05 00:00:00

  • The A+T-rich genome of Herpesvirus saimiri contains a highly conserved gene for thymidylate synthase.

    abstract::Herpesvirus saimiri (HVS) is the prototype member of a distinctive subset of lymphotropic herpesviruses (the gamma 2 subgroup) with A+T-rich coding sequences. In this paper, we show that cells productively infected with HVS contain high concentrations of a virus-specified thymidylate synthase (5,10-methylenetetrahydro...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.11.3604

    authors: Honess RW,Bodemer W,Cameron KR,Niller HH,Fleckenstein B,Randall RE

    更新日期:1986-06-01 00:00:00

  • Phosphorylation-induced conformational dynamics in an intrinsically disordered protein and potential role in phenotypic heterogeneity.

    abstract::Intrinsically disordered proteins (IDPs) that lack a unique 3D structure and comprise a large fraction of the human proteome play important roles in numerous cellular functions. Prostate-Associated Gene 4 (PAGE4) is an IDP that acts as a potentiator of the Activator Protein-1 (AP-1) transcription factor. Homeodomain-I...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1700082114

    authors: Kulkarni P,Jolly MK,Jia D,Mooney SM,Bhargava A,Kagohara LT,Chen Y,Hao P,He Y,Veltri RW,Grishaev A,Weninger K,Levine H,Orban J

    更新日期:2017-03-28 00:00:00

  • Aggregation and disaggregation of senile plaques in Alzheimer disease.

    abstract::We quantitatively analyzed, using laser scanning confocal microscopy, the three-dimensional structure of individual senile plaques in Alzheimer disease. We carried out the quantitative analysis using statistical methods to gain insights about the processes that govern Abeta peptide deposition. Our results show that pl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.14.7612

    authors: Cruz L,Urbanc B,Buldyrev SV,Christie R,Gómez-Isla T,Havlin S,McNamara M,Stanley HE,Hyman BT

    更新日期:1997-07-08 00:00:00

  • A rapid and label-free platform for virus capture and identification from clinical samples.

    abstract::Emerging and reemerging viruses are responsible for a number of recent epidemic outbreaks. A crucial step in predicting and controlling outbreaks is the timely and accurate characterization of emerging virus strains. We present a portable microfluidic platform containing carbon nanotube arrays with differential filtra...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1910113117

    authors: Yeh YT,Gulino K,Zhang Y,Sabestien A,Chou TW,Zhou B,Lin Z,Albert I,Lu H,Swaminathan V,Ghedin E,Terrones M

    更新日期:2020-01-14 00:00:00

  • Mechanism of removal of senescent cells by human macrophages in situ.

    abstract::Mechanisms by which macrophages discriminate between "mature-self" and "senescent-self" were investigated using the human red blood cell (RBC) system as a model. Conditions simulating those encountered in situ were adhered to as closely as possible by using short term culture techniques and incubating with autologous ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.9.3521

    authors: Kay MM

    更新日期:1975-09-01 00:00:00