Interaction of c-Jun Amino-terminal Kinase Interacting Protein-1 with p190 rhoGEF and Its Localization in Differentiated Neurons*

c-Jun amino-terminal kinase (JNK) interacting protein-1 (JIP-1) was originally identified as a cytoplasmic inhibitor of JNK. More recently, JIP-1 was proposed to function as a scaffold protein by complexing specific components of the JNK signaling pathway, namely JNK, mitogen-activated protein kinase kinase 7, and mixed lineage kinase 3. We have identified the human homologue of JIP-1 that contains a phosphotyrosine binding (PTB) domain in addition to a JNK binding domain and an Src homology 3 domain. To identify binding targets for the hJIP-1 PTB domain, a mouse embryo cDNA library was screened using the yeast two-hybrid system. One clone encoded a 191-amino acid region of the neuronal protein rhoGEF, an exchange factor for rhoA. Overexpression of rhoGEF promotes cytoskeletal rearrangement and cell rounding in NIE-115 neuronal cells. The interaction of JIP-1 with rhoGEF was confirmed by coimmunoprecipitation of these proteins from lysates of transiently transfected HEK 293 cells. Using glutathione S-transferase rhoGEF fusion proteins containing deletion or point mutations, we identified a putative PTB binding site within rhoGEF. This binding site does not contain tyrosine, indicating that the JIP PTB domain, like that of Xll α and Numb, binds independently of phosphotyrosine. Several forms of endogenous JIP-1 protein can be detected in neuronal cell lines. Indirect immunofluorescence analysis localized endogenous JIP-1 to the tip of the neurites in differentiated NIE-115 and PC12 cells. The interaction of JIP-1 with rhoGEF and its subcellular localization suggests that JIP-1 may function to specifically localize a signaling complex in neuronal cells.

• Publication year

  1999

• Venue

  Journal of Biological Chemistry

• Publication date

  1999-12-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.274.49.35113PMID 10574993
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Myelin and Collapsin-1 Induce Motor Neuron Growth Cone Collapse through Different Pathways: Inhibition of Collapse by Opposing Mutants of Rac1

  1999cited by this paper
• The Dbl-related Protein, Lfc, Localizes to Microtubules and Mediates the Activation of Rac Signaling Pathways in Cells*

  1999cited by this paper
• Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/c-Jun-amino-terminal kinase interacting protein-1 (JIP-1) gene.

  1999cited by this paper
• IB1, a JIP-1-related Nuclear Protein Present in Insulin-secreting Cells*

  1998cited by this paper
• Microinjection of activated phosphatidylinositol-3 kinase induces process outgrowth in rat PC12 cells through the Rac-JNK signal transduction pathway.

  1998cited by this paper
• A mammalian scaffold complex that selectively mediates MAP kinase activation.

  1998cited by this paper
• Numb-Associated Kinase Interacts with the Phosphotyrosine Binding Domain of Numb and Antagonizes the Function of Numb In Vivo

  1998cited by this paper
• Differential regulation of c‐Jun by ERK and JNK during PC12 cell differentiation

  1998cited by this paper
• The Mammalian Numb Phosphotyrosine-binding Domain

  1998cited by this paper
• Functional Analysis of the Numb Phosphotyrosine-binding Domain Using Site-directed Mutagenesis*

  1998cited by this paper
• Activation of RhoA and SAPK/JNK signalling pathways by the RhoA‐specific exchange factor mNET1

  1998cited by this paper
• A cytoplasmic inhibitor of the JNK signal transduction pathway.

  1997cited by this paper
• Role of Actin Polymerization and Adhesion to Extracellular Matrix in Rac- and Rho-induced Cytoskeletal Reorganization

  1997cited by this paper
• Dissociation of LPA-induced cytoskeletal contraction from stress fiber formation by differential localization of RhoA.

  1997cited by this paper
• Identification of a Novel, Putative Rho-specific GDP/GTP Exchange Factor and a RhoA-binding Protein: Control of Neuronal Morphology

  1997cited by this paper
• Rho GTPases and signaling networks.

  1997cited by this paper
• Expression of a Constitutively Active Phosphatidylinositol 3-Kinase Induces Process Formation in Rat PC12 Cells

  1997cited by this paper
• Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42.

  1997cited by this paper
• Specific Activation of a c-Jun NH2-terminal Kinase Isoform and Induction of Neurite Outgrowth in PC-12 Cells by Staurosporine*

  1997cited by this paper
• Rho family GTPases: the cytoskeleton and beyond.

  1996cited by this paper
• The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein

  1996cited by this paper
• Sphingosine‐1‐phosphate rapidly induces Rho‐dependent neurite retraction: action through a specific cell surface receptor.

  1996cited by this paper
• Identification of residues that control specific binding of the Shc phosphotyrosine-binding domain to phosphotyrosine sites.

  1996cited by this paper
• Identification of Residues within the SHC Phosphotyrosine Binding/Phosphotyrosine Interaction Domain Crucial for Phosphopeptide Interaction (*)

  1996cited by this paper
• GTPase-deficient G alpha 16 and G alpha q induce PC12 cell differentiation and persistent activation of cJun NH2-terminal kinases

  1996cited by this paper
• Ras-Raf interaction: two-hybrid analysis.

  1995cited by this paper
• Structure and ligand recognition of the phosphotyrosine binding domain of Shc

  1995cited by this paper
• The phosphotyrosine interaction domain of Shc binds an LXNPXY motif on the epidermal growth factor receptor

  1995cited by this paper
• Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain

  1995cited by this paper
• A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors.

  1994cited by this paper
• An alternative to SH2 domains for binding tyrosine-phosphorylated proteins.

  1994cited by this paper
• Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho

  1994cited by this paper
• The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.

  1993cited by this paper
• Lysophosphatidic acid induces neuronal shape changes via a novel, receptor-mediated signaling pathway: similarity to thrombin action.

  1993cited by this paper
• The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit.

  1993cited by this paper
• High-efficiency transformation of mammalian cells by plasmid DNA.

  1987cited by this paper

• c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy

  2025cites this paper
• Protective effect of cornuside on OGD/R injury in SH-SY5Y cells and its underlying mechanism.

  2023cites this paper
• Low-Density Lipoprotein Receptor-Related Protein 8 at the Crossroad between Cancer and Neurodegeneration

  2022cites this paper
• Expression of a RhoA-Specific Guanine Nucleotide Exchange Factor, p190RhoGEF, in Mouse Macrophages Negatively Affects M1 Polarization and Inflammatory Responses

  2022cites this paper
• Intrinsic disorder in proteins associated with oxidative stress-induced JNK signaling

  2021cites this paper
• Resurgence of phosphotyrosine binding domains: Structural and functional properties essential for understanding disease pathogenesis.

  2021cites this paper
• Computational modelling of protein-protein and cell-cell interaction across multiple scales

  2018cites this paper
• Direct regulation of p190RhoGEF by activated Rho and Rac GTPases.

  2018cites this paper
• Characterization of the binding mode of JNK-interacting protein 1 (JIP1) to kinesin-light chain 1 (KLC1)

  2018cites this paper
• Requirement of JIP 1-Mediated c-Jun N-Terminal Kinase Activation for Obesity-Induced Insulin Resistance §

  2017cites this paper
• Phosphorylation of KLC1 modifies interaction with JIP1 and abolishes the enhanced fast velocity of APP transport by kinesin-1

  2017cites this paper
• JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

  2016cites this paper
• MAP Kinase Modules in Signaling

  2014cites this paper
• JIP1 Mediates Anterograde Transport of Rab10 Cargos during Neuronal Polarization

  2014cites this paper
• Src Homology 2 Domain Containing Protein 5 (SH2D5) Binds the Breakpoint Cluster Region Protein, BCR, and Regulates Levels of Rac1-GTP*

  2014cites this paper
• The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases

  2014cites this paper
• New insights into the MAPK function in meiotic progression and the regulation of osmostress-induced apoptosis in Xenopus oocytes

  2014cites this paper
• Computational Modeling Reveals Optimal Strategy for Kinase Transport by Microtubules to Nerve Terminals

  2014cites this paper
• Role of ARF6 in breast cancer cell invasion

  2014cites this paper
• RhoGEFs in cell motility: novel links between Rgnef and focal adhesion kinase.

  2014cites this paper
• The interaction of Kinesin-1 with its adaptor protein JIP1 can be regulated via proteins binding to the JIP1-PTB domain

  2013influential citation
• Rgnef (p190RhoGEF) Knockout Inhibits RhoA Activity, Focal Adhesion Establishment, and Cell Motility Downstream of Integrins

  2012cites this paper
• A study of the molecular interactions between kinesin motor proteins and the TRAK family of kinesin adaptors

  2012cites this paper
• Increased p190RhoGEF expression in activated B cells correlates with the induction of the plasma cell differentiation

  2011cites this paper
• G-Protein-Coupled Receptors, Signal Fidelity, and Cell Transformation

  2010cites this paper
• Posttranslational Modifications of Tubulin and the Polarized Transport of Kinesin-1 in Neurons

  2010cites this paper
• JIP1 binding to RBP-Jk mediates cross-talk between the Notch1 and JIP1-JNK signaling pathway

  2010cites this paper
• Requirement of JIP1-Mediated c-Jun N-Terminal Kinase Activation for Obesity-Induced Insulin Resistance

  2010cites this paper
• Reelin and apolipoprotein E receptor 2 in the embryonic and mature brain: effects of an evolutionary change in the apoER2 gene

  2010cites this paper
• The role of scaffold proteins in JNK signalling

  2010cites this paper
• Mammalian MAP Kinases

  2010cites this paper
• Mitogen-Activated Protein Kinases and Their Scaffolding Proteins

  2010cites this paper
• Regulation of stress-associated scaffold proteins JIP1 and JIP3 on the c-Jun NH2-terminal kinase in ischemia-reperfusion.

  2010cites this paper
• Establishment of axon-dendrite polarity in developing neurons.

  2009cites this paper
• The role of microtubules in initial neuronal polarization

  2008influential citation
• Kinesin regulation: Discovering the mechanisms that mediate autoinhibition, cargo complex formation, and selective microtubule use in neurons

  2008cites this paper
• MAP kinase pathways in neuronal cell death.

  2008cites this paper
• "JIP"ing along the axon: the complex roles of JIPs in axonal transport.

  2008cites this paper
• Delta-catenin-induced dendritic morphogenesis. An essential role of p190RhoGEF interaction through Akt1-mediated phosphorylation.

  2008cites this paper
• Co‐operative Versus Independent Transport of Different Cargoes by Kinesin‐1

  2008cites this paper
• Regulatory mechanisms of mitogen-activated kinase signaling

  2007cites this paper
• ROCK and Rho: Biochemistry and Neuronal Functions of Rho-Associated Protein Kinases

  2007cites this paper
• Scaffold proteins of MAP-kinase modules

  2007cites this paper
• Similarities and differences between the Wnt and reelin pathways in the forming brain

  2007cites this paper
• Low-Density Lipoprotein Receptor-Related Protein 8 (LRP8) Is Upregulated in Granulosa Cells of Bovine Dominant Follicle: Molecular Characterization and Spatio-Temporal Expression Studies1

  2007cites this paper
• The JNK signal transduction pathway.

  2007cites this paper
• The bright side of JNKs-Multitalented mediators in neuronal sprouting, brain development and nerve fiber regeneration.

  2006cites this paper
• Regulation of expression and signalling modulator function of mammalian tribbles is cell-type specific.

  2006cites this paper
• Microtubule acetylation promotes kinesin-1 binding and transport.

  2006cites this paper
• Regulation of the actin cytoskeleton by ephrin-B signalling

  2006influential citation
• Multiple domain 'nexus' proteins in receptor-mediated cell signaling

  2006cites this paper
• INTEGRACIÓN DE LA FUNCIÓN DE VRK2 EN LAS RUTAS DE SEÑALIZACIÓN DE JNK Y P53.

  2006cites this paper
• A molecular basis for differential Ca2+ signalling in B lymphocytes

  2006cites this paper
• Characterisation of the physical and functional interaction of DRhoGEF2 with DMec2 via its PDZ domain

  2006cites this paper
• JSAP1 is required for the cell adhesion and spreading of mouse embryonic fibroblasts.

  2006cites this paper
• Scaffold proteins in MAP kinase signaling: more than simple passive activating platforms

  2006cites this paper
• Membrane and juxtamembrane targeting by PH and PTB domains.

  2006cites this paper
• Transformation by the Rho-specific Guanine Nucleotide Exchange Factor Dbs Requires ROCK I-mediated Phosphorylation of Myosin Light Chain*

  2006cites this paper
• Cdc24 Regulates Nuclear Shuttling and Recruitment of the Ste5 Scaffold to a Heterotrimeric G Protein in Saccharomyces cerevisiae*

  2005cites this paper
• Missense mutations resulting in type 1 lissencephaly

  2005cites this paper
• Increased JNK phosphorylation and oxidative stress in response to increased glucose flux through increased GLUT1 expression in rat retinal endothelial cells.

  2005cites this paper
• Wsh3/Tea4 is a novel cell-end factor essential for bipolar distribution of Tea1 and protects cell polarity under environmental stress in S. pombe.

  2005cites this paper
• RNA-binding protein is involved in aggregation of light neurofilament protein and is implicated in the pathogenesis of motor neuron degeneration

  2005cites this paper
• Wsh3/Tea4 is a novel cell-end factor essential for bipolar distribution of Tea1 and protects cell polarity under environmental stress in fission yeast

  2005cites this paper
• Association of CNK1 with Rho guanine nucleotide exchange factors controls signaling specificity downstream of Rho.

  2005cites this paper
• Coordinated transport of phosphorylated amyloid-β precursor protein and c-Jun NH2-terminal kinase–interacting protein-1

  2005influential citation
• Review Missense mutations resulting in type 1 lissencephaly

  2005cites this paper
• JIP1 regulates neuronal apoptosis in response to stress.

  2005cites this paper
• Investigation of TSGA10 gene expression, localisation and protein interaction in human and mouse spermatogenesis.

  2005cites this paper
• Retrograde axonal transport of JNK signaling molecules influence injury induced nuclear changes in p-c-Jun and ATF3 in adult rat sensory neurons.

  2005cites this paper
• RNA-binding protein is involved in aggregation of light neurofilament protein and is implicated in the pathogenesis of motor neuron degeneration.

  2005cites this paper
• The axon guidance defect of the telencephalic commissures of the JSAP1-deficient brain was partially rescued by the transgenic expression of JIP1.

  2005cites this paper
• Molecular motors and mechanisms of directional transport in neurons

  2005cites this paper
• DCXs Phosphorylation by Not Just aNother Kinase (JNK)

  2004cites this paper
• Thyrotropin-releasing hormone-stimulated thyrotropin expression involves islet-brain-1/c-Jun N-terminal kinase interacting protein-1.

  2004cites this paper
• Islet-brain (IB)/JNK-interacting proteins (JIPs): future targets for the treatment of neurodegenerative diseases?

  2004cites this paper
• LRP and PDGF signaling: a pathway to atherosclerosis.

  2004cites this paper
• Cytoplasmic tail adaptors of alzheimer’s amyloid-β protein precursor

  2004cites this paper
• Cytoplasmic tail adaptors of Alzheimer's amyloid-beta protein precursor.

  2004cites this paper
• Neuronal migration and the role of reelin during early development of the cerebral cortex

  2004cites this paper
• DCX, a new mediator of the JNK pathway

  2004influential citation
• Pleckstrin Homology and Phosphotyrosine-binding Domain-dependent Membrane Association and Tyrosine Phosphorylation of Dok-4, an Inhibitory Adapter Molecule Expressed in Epithelial Cells*

  2004cites this paper
• Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death

  2004influential citation
• Repression of phospho‐JNK and infarct volume in ischemic brain of JIP1‐deficient mice

  2003influential citation
• Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

  2003cites this paper
• Cutting Edge: Induced Expression of a RhoA-Specific Guanine Nucleotide Exchange Factor, p190RhoGEF, Following CD40 Stimulation and WEHI 231 B Cell Activation1

  2003cites this paper
• Recruitment of JNK to JIP1 and JNK-dependent JIP1 Phosphorylation Regulates JNK Module Dynamics and Activation*

  2003cites this paper
• Cytoplasmic retention sites in p190RhoGEF confer anti-apoptotic activity to an EGFP-tagged protein.

  2003cites this paper
• The scaffold protein IB1/JIP-1 is a critical mediator of cytokine-induced apoptosis in pancreatic β cells

  2003cites this paper
• Increased vulnerability to kainic acid‐induced epileptic seizures in mice underexpressing the scaffold protein Islet‐Brain 1/JIP‐1

  2003cites this paper
• The Role of c‐Jun N‐Terminal Kinase (JNK) in Parkinson's Disease

  2003cites this paper
• Molecular recognitions in the MAP kinase cascades.

  2003cites this paper
• Trafficking of signaling modules by kinesin motors

  2003cites this paper
• Regulation of MAP kinase signaling modules by scaffold proteins in mammals.

  2003cites this paper
• The JNK-interacting Protein-1 Scaffold Protein Targets MAPK Phosphatase-7 to Dephosphorylate JNK*

  2003cites this paper
• Direct Interaction of Focal Adhesion Kinase with p190RhoGEF*

  2003cites this paper
• CHAPTER 218 – G-Protein-Coupled Receptors, Cell Transformation, and Signal Fidelity

  2003cites this paper
• Chapter 184 - X c,v Mammalian MAP Kinases

  2003cites this paper
• Interaction of Alzheimer's β-Amyloid Precursor Family Proteins with Scaffold Proteins of the JNK Signaling Cascade*

  2002cites this paper
• Akt1 regulates a JNK scaffold during excitotoxic apoptosis.

  2002cites this paper