Spatiotemporally regulated protein kinase A activity is a critical regulator of growth factor-stimulated extracellular signal-regulated kinase signaling in PC12 cells.

Abstract:

:PC12 cells exhibit precise temporal control of growth factor signaling in which stimulation with epidermal growth factor (EGF) leads to transient extracellular signal-regulated kinase (ERK) activity and cell proliferation, whereas nerve growth factor (NGF) stimulation leads to sustained ERK activity and differentiation. While cyclic AMP (cAMP)-mediated signaling has been shown to be important in conferring the sustained ERK activity achieved by NGF, little is known about the regulation of cAMP and cAMP-dependent protein kinase (PKA) in these cells. Using fluorescence resonance energy transfer (FRET)-based biosensors localized to discrete subcellular locations, we showed that both NGF and EGF potently activate PKA at the plasma membrane, although they generate temporally distinct activity patterns. We further show that both stimuli fail to induce cytosolic PKA activity and identify phosphodiesterase 3 (PDE3) as a critical regulator in maintaining this spatial compartmentalization. Importantly, inhibition of PDE3, and thus perturbation of the spatiotemporal regulation of PKA activity, dramatically increases the duration of EGF-stimulated nuclear ERK activity in a PKA-dependent manner. Together, these findings identify EGF and NGF as potent activators of PKA activity specifically at the plasma membrane and reveal a novel regulatory mechanism contributing to the growth factor signaling specificity achieved by NGF and EGF in PC12 cells.

journal_name

Mol Cell Biol

authors

Herbst KJ,Allen MD,Zhang J

doi

10.1128/MCB.05459-11

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

4063-75

issue

19

eissn

0270-7306

issn

1098-5549

pii

MCB.05459-11

journal_volume

31

pub_type

杂志文章
  • Negative regulatory gene for general control of amino acid biosynthesis in Saccharomyces cerevisiae.

    abstract::In Saccharomyces cerevisiae, many amino acid biosynthetic pathways are coregulated by a complex general control system: starvation for a single amino acid results in the derepression of amino acid biosynthetic genes in multiple pathways. Derepression of these genes is mediated by positive (GCN) and negative (GCD) regu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.9.3150

    authors: Myers PL,Skvirsky RC,Greenberg ML,Greer H

    更新日期:1986-09-01 00:00:00

  • Expression of human alpha-tubulin genes: interspecies conservation of 3' untranslated regions.

    abstract::To examine the sequence complexity and differential expression of human alpha-tubulin genes, we constructed cDNA libraries from two unrelated tissue types (epidermis and fetal brain). The complete sequence of a positively hybridizing alpha-tubulin clone from each library is described. Each is shown to represent an abu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.10.1738

    authors: Cowan NJ,Dobner PR,Fuchs EV,Cleveland DW

    更新日期:1983-10-01 00:00:00

  • A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

    abstract::Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00594-15

    authors: Mir RA,Bele A,Mirza S,Srivastava S,Olou AA,Ammons SA,Kim JH,Gurumurthy CB,Qiu F,Band H,Band V

    更新日期:2015-12-28 00:00:00

  • Pi, a pre-B-cell-specific enhancer element in the immunoglobulin heavy-chain enhancer.

    abstract::We have identified a new immunoglobulin heavy-chain enhancer element, designated pi, between the microE2 and microE3 elements. The pi enhancer element is transcriptionally active primarily during early stages of B-cell development but becomes virtually inactive during B-cell maturation at about the stage of immunoglob...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.10.5957

    authors: Libermann TA,Baltimore D

    更新日期:1993-10-01 00:00:00

  • Identification of an upstream activating sequence and an upstream repressible sequence of the pyruvate kinase gene of the yeast Saccharomyces cerevisiae.

    abstract::To clarify carbon source-dependent control of the glycolytic pathway in the yeast Saccharomyces cerevisiae, we have initiated a study of transcriptional regulation of the pyruvate kinase gene (PYK). By deletion analysis of the 5'-noncoding region of the PYK gene, we have identified an upstream activating sequence (UAS...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.2.442

    authors: Nishizawa M,Araki R,Teranishi Y

    更新日期:1989-02-01 00:00:00

  • Identification of a novel isoform of the retinoic acid receptor gamma expressed in the mouse embryo.

    abstract::Retinoic acid is known to have profound effects on developmental processes. It has been implicated as a putative morphogen in the developing chick limb bud and regenerating amphibian limb blastema and has been demonstrated to have powerful teratogenic effects in mammals, including humans. Recently, three specific reti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.5.2335

    authors: Giguère V,Shago M,Zirngibl R,Tate P,Rossant J,Varmuza S

    更新日期:1990-05-01 00:00:00

  • A novel functional human eukaryotic translation initiation factor 4G.

    abstract::Mammalian eukaryotic translation initiation factor 4F (eIF4F) is a cap-binding protein complex consisting of three subunits: eIF4E, eIF4A, and eIF4G. In yeast and plants, two related eIF4G species are encoded by two different genes. To date, however, only one functional eIF4G polypeptide, referred to here as eIF4GI, h...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.1.334

    authors: Gradi A,Imataka H,Svitkin YV,Rom E,Raught B,Morino S,Sonenberg N

    更新日期:1998-01-01 00:00:00

  • SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na(+)-K(+)-Cl(-) cotransporter 2.

    abstract::Proper control of NaCl excretion in the kidney is central to bodily functions, yet many mechanisms that regulate reabsorption of sodium and chloride in the kidney remain incompletely understood. Here, we identify an important role played by the intracellular sorting receptor SORLA (sorting protein-related receptor wit...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01560-09

    authors: Reiche J,Theilig F,Rafiqi FH,Carlo AS,Militz D,Mutig K,Todiras M,Christensen EI,Ellison DH,Bader M,Nykjaer A,Bachmann S,Alessi D,Willnow TE

    更新日期:2010-06-01 00:00:00

  • A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function.

    abstract::Mammalian MEK1 and MEK2 contain a proline-rich (PR) sequence that is absent both from the yeast homologs Ste7 and Byr1 and from a recently cloned activator of the JNK/stress-activated protein kinases, SEK1/MKK4. Since this PR sequence occurs in MEKs that are regulated by Raf family enzymes but is missing from MEKs and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.10.5214

    authors: Catling AD,Schaeffer HJ,Reuter CW,Reddy GR,Weber MJ

    更新日期:1995-10-01 00:00:00

  • Ras-specific exchange factor GRF: oligomerization through its Dbl homology domain and calcium-dependent activation of Raf.

    abstract::The full-length versions of the Ras-specific exchange factors Ras-GRF1 (GRF1) and Ras-GRF2 (GRF2), which are expressed in brain and a restricted number of other organs, possess an ionomycin-dependent activation of Erk mitogen-activated protein kinase activity in 293T cells (C. L. Farnsworth et al., Nature 376:524-527,...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.7.4611

    authors: Anborgh PH,Qian X,Papageorge AG,Vass WC,DeClue JE,Lowy DR

    更新日期:1999-07-01 00:00:00

  • Ptc1, a type 2C Ser/Thr phosphatase, inactivates the HOG pathway by dephosphorylating the mitogen-activated protein kinase Hog1.

    abstract::The HOG (high-osmolarity glycerol) mitogen-activated protein kinase (MAPK) pathway regulates the osmotic stress response in the yeast Saccharomyces cerevisiae. Three type 2C Ser/Thr phosphatases (PTCs), Ptc1, Ptc2, and Ptc3, have been isolated as negative regulators of this pathway. Previously, multicopy expression of...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.1.51-60.2001

    authors: Warmka J,Hanneman J,Lee J,Amin D,Ota I

    更新日期:2001-01-01 00:00:00

  • Evolutionary conservation and predicted structure of the Drosophila extra sex combs repressor protein.

    abstract::The Drosophila extra sex combs (esc) protein, a member of the Polycomb group (PcG), is a transcriptional repressor of homeotic genes. Genetic studies have shown that esc protein is required in early embryos at about the time that other PcG proteins become engaged in homeotic gene repression. The esc protein consists p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.11.6663

    authors: Ng J,Li R,Morgan K,Simon J

    更新日期:1997-11-01 00:00:00

  • RBM4 Regulates Neuronal Differentiation of Mesenchymal Stem Cells by Modulating Alternative Splicing of Pyruvate Kinase M.

    abstract::RBM4 promotes differentiation of neuronal progenitor cells and neurite outgrowth of cultured neurons via its role in splicing regulation. In this study, we further explored the role of RBM4 in neuronal differentiation. During neuronal differentiation, energy production shifts from glycolysis to oxidative phosphorylati...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00466-16

    authors: Su CH,Hung KY,Hung SC,Tarn WY

    更新日期:2017-01-19 00:00:00

  • Self-association of the Gal4 inhibitor protein Gal80 is impaired by Gal3: evidence for a new mechanism in the GAL gene switch.

    abstract::The DNA-binding transcriptional activator Gal4 and its regulators Gal80 and Gal3 constitute a galactose-responsive switch for the GAL genes of Saccharomyces cerevisiae. Gal4 binds to GAL gene UASGAL (upstream activation sequence in GAL gene promoter) sites as a dimer via its N-terminal domain and activates transcripti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00646-12

    authors: Egriboz O,Goswami S,Tao X,Dotts K,Schaeffer C,Pilauri V,Hopper JE

    更新日期:2013-09-01 00:00:00

  • Rates of mutation to growth factor autonomy and tumorigenicity differ in hematopoietic stem and precursor cells expressing the multilineage colony-stimulating factor gene.

    abstract::At least two separate but interdependent events are required to attain autonomous growth as a consequence of ectopic expression of the multilineage colony-stimulating factor gene in hematopoietic progenitor cells. The rate at which the second event occurs is more than 3 orders of magnitude higher in precursor cell lin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.12.5746

    authors: Laker C,Kluge N,Stocking C,Just U,Franz MJ,Ostertag W,DeLamarter JF,Dexter M,Spooncer E

    更新日期:1989-12-01 00:00:00

  • Effects of the SANT domain of tension-induced/inhibited proteins (TIPs), novel partners of the histone acetyltransferase p300, on p300 activity and TIP-6-induced adipogenesis.

    abstract::We previously identified a set of transcription regulators, referred to as TIPs (tension-induced/inhibited proteins), with a role in myogenic versus adipogenic differentiation. Here we report that the TIP family comprises eight isoforms, all bearing a SANT (switching-defective protein 3, adaptor 2, nuclear receptor co...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00333-08

    authors: Badri KR,Zhou Y,Dhru U,Aramgam S,Schuger L

    更新日期:2008-10-01 00:00:00

  • Exploring functional redundancy in the immunoglobulin mu heavy-chain gene enhancer.

    abstract::Immunoglobulin (Ig) mu heavy-chain gene enhancer activity is mediated by multiple DNA binding proteins. Mutations of several protein binding sites in the enhancer do not affect enhancer activity significantly. This feature, termed redundancy, is thought to be due to functional compensation of the mutated sites by othe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.11.6870

    authors: Dang W,Nikolajczyk BS,Sen R

    更新日期:1998-11-01 00:00:00

  • Direct interaction with Rab11a targets the epithelial Ca2+ channels TRPV5 and TRPV6 to the plasma membrane.

    abstract::TRPV5 and TRPV6 are the most Ca2+-selective members of the transient receptor potential (TRP) family of cation channels and play a pivotal role in the maintenance of Ca2+ balance in the body. However, little is known about the mechanisms controlling the plasma membrane abundance of these channels to regulate epithelia...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.1.303-312.2006

    authors: van de Graaf SF,Chang Q,Mensenkamp AR,Hoenderop JG,Bindels RJ

    更新日期:2006-01-01 00:00:00

  • RPD1 (SIN3/UME4) is required for maximal activation and repression of diverse yeast genes.

    abstract::We show that the extent of transcriptional regulation of many, apparently unrelated, genes in Saccharomyces cerevisiae is dependent on RPD1 (and RPD3 [M. Vidal and R. F. Gaber, Mol. Cell. Biol. 11:6317-6327, 1991]). Genes regulated by stimuli as diverse as external signals (PHO5), cell differentiation processes (SPO11...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.12.6306

    authors: Vidal M,Strich R,Esposito RE,Gaber RF

    更新日期:1991-12-01 00:00:00

  • Activation of a late H2B histone gene in blastula-stage sea urchin embryos by an unusual enhancer element located 3' of the gene.

    abstract::In the sea urchin embryo, late histone genes are transcribed at low levels during cleavage and blastula formation and at substantially higher levels in later stages of embryogenesis. To investigate the molecular basis of the stage-specific expression of a late H2B histone gene, we injected mutant genes lacking portion...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.12.6730

    authors: Zhao AZ,Colin AM,Bell J,Baker M,Char BR,Maxson R

    更新日期:1990-12-01 00:00:00

  • Interference between proteins Hap46 and Hop/p60, which bind to different domains of the molecular chaperone hsp70/hsc70.

    abstract::Several structurally divergent proteins associate with molecular chaperones of the 70-kDa heat shock protein (hsp70) family and modulate their activities. We investigated the cofactors Hap46 and Hop/p60 and the effects of their binding to mammalian hsp70 and the cognate form hsc70. Hap46 associates with the amino-term...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.11.6238

    authors: Gebauer M,Zeiner M,Gehring U

    更新日期:1998-11-01 00:00:00

  • Gab1 is an integrator of cell death versus cell survival signals in oxidative stress.

    abstract::Upon the addition of different growth factors and cytokines, the Gab1 docking protein is tyrosine phosphorylated and in turn activates different signaling pathways. On the basis of the large body of evidence concerning cross talk between the signaling pathways activated by growth factors and oxidative stress, we decid...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.13.4471-4484.2003

    authors: Holgado-Madruga M,Wong AJ

    更新日期:2003-07-01 00:00:00

  • Severe alterations of cerebellar cortical development after constitutive activation of Wnt signaling in granule neuron precursors.

    abstract::The Wnt/β-catenin signaling pathway plays crucial roles in early hindbrain formation, and its constitutive activity is associated with a subset of human medulloblastoma, a malignant childhood tumor of the posterior fossa. However, the precise function of Wnt/β-catenin signaling during cerebellar development is still e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.05718-11

    authors: Lorenz A,Deutschmann M,Ahlfeld J,Prix C,Koch A,Smits R,Fodde R,Kretzschmar HA,Schüller U

    更新日期:2011-08-01 00:00:00

  • SWI-SNF-mediated nucleosome remodeling: role of histone octamer mobility in the persistence of the remodeled state.

    abstract::SWI-SNF is an ATP-dependent chromatin remodeling complex that disrupts DNA-histone interactions. Several studies of SWI-SNF activity on mononucleosome substrates have suggested that remodeling leads to novel, accessible nucleosomes which persist in the absence of continuous ATP hydrolysis. In contrast, we have reporte...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.9.3058-3068.2000

    authors: Jaskelioff M,Gavin IM,Peterson CL,Logie C

    更新日期:2000-05-01 00:00:00

  • AMPK Promotes Aberrant PGC1β Expression To Support Human Colon Tumor Cell Survival.

    abstract::A major goal of cancer research is the identification of tumor-specific vulnerabilities that can be exploited for the development of therapies that are selectively toxic to the tumor. We show here that the transcriptional coactivators peroxisome proliferator-activated receptor gamma coactivator 1β (PGC1β) and estrogen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00528-15

    authors: Fisher KW,Das B,Kim HS,Clymer BK,Gehring D,Smith DR,Costanzo-Garvey DL,Fernandez MR,Brattain MG,Kelly DL,MacMillan J,White MA,Lewis RE

    更新日期:2015-11-01 00:00:00

  • A Novel Regulatory Axis, CHD1L-MicroRNA 486-Matrix Metalloproteinase 2, Controls Spermatogonial Stem Cell Properties.

    abstract::Spermatogonial stem cells (SSCs) are unipotent germ cells that are at the foundation of spermatogenesis and male fertility. However, the underlying molecular mechanisms governing SSC stemness and growth properties remain elusive. We have recently identified chromodomain helicase/ATPase DNA binding protein 1-like (Chd1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00357-18

    authors: Liu SS,Maguire EM,Bai YS,Huang L,Liu Y,Xu L,Fauzi I,Zhang SQ,Xiao Q,Ma NF

    更新日期:2019-02-04 00:00:00

  • Organizational analysis of elav gene and functional analysis of ELAV protein of Drosophila melanogaster and Drosophila virilis.

    abstract::Drosophila virilis genomic DNA corresponding to the D. melanogaster embryonic lethal abnormal visual system (elav) locus was cloned. DNA sequence analysis of a 3.8-kb genomic piece allowed identification of (i) an open reading frame (ORF) with striking homology to the previously identified D. melanogaster ORF and (ii)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.6.2994

    authors: Yao KM,White K

    更新日期:1991-06-01 00:00:00

  • Phosphorylation of TFIIA stimulates TATA binding protein-TATA interaction and contributes to maximal transcription and viability in yeast.

    abstract::Posttranslational modification of general transcription factors may be an important mechanism for global gene regulation. The general transcription factor IIA (TFIIA) binds to the TATA binding protein (TBP) and is essential for high-level transcription mediated by various activators. Modulation of the TFIIA-TBP intera...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.4.2846

    authors: Solow SP,Lezina L,Lieberman PM

    更新日期:1999-04-01 00:00:00

  • ClipR-59 interacts with Akt and regulates Akt cellular compartmentalization.

    abstract::Akt is activated on the plasma membrane and its substrates are distributed throughout various cellular compartments. To phosphorylate its substrates, Akt needs to be recruited to specific intracellular compartments. Thus, regulation of Akt cellular compartmentalization constitutes an important mechanism to specify Akt...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00754-08

    authors: Ding J,Du K

    更新日期:2009-03-01 00:00:00

  • Phosphoinositide-dependent kinase 1 and mTORC2 synergistically maintain postnatal heart growth and heart function in mice.

    abstract::The protein kinase Akt plays a critical role in heart function and is activated by phosphorylation of threonine 308 (T308) and serine 473 (S473). While phosphoinositide-dependent kinase 1 (PDK1) is responsible for Akt T308 phosphorylation, the identities of the kinases for Akt S473 phosphorylation in the heart remain ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00144-14

    authors: Zhao X,Lu S,Nie J,Hu X,Luo W,Wu X,Liu H,Feng Q,Chang Z,Liu Y,Cao Y,Sun H,Li X,Hu Y,Yang Z

    更新日期:2014-06-01 00:00:00