JLP-centrosome is essential for the microtubule-mediated nucleocytoplasmic transport induced by extracellular stimuli.

JLP belongs to the JIP family whose members serve as scaffolding proteins that link motor proteins and their cargo for intracellular transport. Although JLP is mainly cytoplasmic, it accumulates as a focus in the perinuclear region when stimulated by extracellular stimuli. Focus formation, which changes the nucleus shape and concentrates the nuclear pores, depends on p38MAPK activation and the dynein retrograde motor protein complex.

Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells.

c-Myc is a highly pleiotropic transcription factor known to control cell cycle progression, apoptosis, and cellular transformation. Normally, ectopic expression of c-Myc is associated with promoting cell proliferation or triggering cell death via activating p53. However, it is not clear how the levels of c-Myc lead to different cellular responses.

Identification of Kinesin-1 Cargos Using Fluorescence Microscopy.

Fluorescence microscopy is employed to identify Kinesin-1 cargos. Recently, the heavy chain of Kinesin-1 (KIF5B) was shown to transport the nuclear transcription factor c-MYC for proteosomal degradation in the cytoplasm. The method described here involves the study of a motorless KIF5B mutant for fluorescence microscopy.

JNK-associated Leucine Zipper Protein Functions as a Docking Platform for Polo-like Kinase 1 and Regulation of the Associating Transcription Factor Forkhead Box Protein K1.

JLP (JNK-associated leucine zipper protein) is a scaffolding protein that interacts with various signaling proteins associated with coordinated regulation of cellular process such as endocytosis, motility, neurite outgrowth, cell proliferation, and apoptosis. Here we identified PLK1 (Polo-like kinase 1) as a novel interaction partner of JLP through mass spectrometric approaches. Our results indicate that JLP is phospho-primed by PLK1 on Thr-351, which is recognized by the Polo box domain of PLK1 leading to phosphorylation of JLP at additional sites.

Transport of c-MYC by Kinesin-1 for proteasomal degradation in the cytoplasm.

c-MYC is an oncogenic transcription factor that is degraded by the proteasome pathway. However, the mechanism that regulates delivery of c-MYC to the proteasome for degradation is not well characterized. Here, the results show that the motor protein complex Kinesin-1 transports c-MYC to the cytoplasm for proteasomal degradation.

A novel role of the scaffolding protein JLP in tuning CD40-induced activation of dendritic cells.

Receptor internalization is a common mechanism underlying surface receptor down-regulation (and thus receptor signaling) upon its engagement with the cognate ligand. Tight regulation of surface CD40 expression is critical in regulating different functional properties of dendritic cell (DC). Engagement of CD40 on mature DC and the cognate CD40 ligand on T cell activates c-Jun N-terminal MAPK, p38 and ERK1/2 MAPK pathways in mature DC.

(Z)-1-aryl-3-arylamino-2-propen-1-ones, highly active stimulators of tubulin polymerization: synthesis, structure-activity relationship (SAR), tubulin polymerization, and cell growth inhibition studies.

Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values.

Neoplastic transformation induced by the gep oncogenes involves the scaffold protein JNK-interacting leucine zipper protein.

The activated mutants of the α-subunits of G proteins G(12) and G(13) have been designated as the gep oncogenes owing to their ability to stimulate diverse oncogenic signaling pathways that lead to neoplastic transformation of fibroblast cell lines and tumorigenesis in nude mice models. Studies from our laboratory as well as others have shown that the growth-promoting activities of Gα(12) and Gα(13) involve potent activation of c-Jun N-terminal kinases (JNKs). Our previous studies have indicated that the JNK-interacting leucine zipper protein (JLP), a scaffold protein involved in the structural and functional organization of the JNK/p38 mitogen-activated protein kinase module, tethers Gα(12) and Gα(13) to the JNK signaling module.

Regulation of neurite outgrowth by interactions between the scaffolding protein, JNK-associated leucine zipper protein, and neuronal growth-associated protein superior cervical ganglia clone 10.

JLP (JNK-associated leucine zipper protein) is a novel scaffolding protein involved in JNK signaling. Although it is known that JLP is highly expressed in brain, the biological function of JLP in neuronal systems remains unknown. Here, we report a novel interaction between JLP and SCG10 (superior cervical ganglia clone 10), which is a microtubule-destabilizing factor that is essential for neurite outgrowth.

Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation.

Short-type PB-cadherin promotes self-renewal of spermatogonial stem cells via multiple signaling pathways.

Stem cells represent a unique population of cells with self-renewal capacity. However, the molecular control of self-renewal and differentiation of stem cells has remained enigmatic. Here, we show that short-type PB-cadherin (STPB-C) promoted self-renewal of spermatogonial stem cells (SSCs) via activating Janus kinase/signal transducer and activator of transcription (JAK-STAT) and phosphoinositide-3 kinase (PI3-K)/Akt, and blocking transforming growth factor (TGF)-beta1 signaling.

Activation of p38alpha/beta MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo.

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cell differentiation, but the signaling mechanisms by which it is activated during this process are largely unknown. Cdo is an immunoglobulin superfamily member that functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that the Cdo intracellular region interacts with JLP, a scaffold protein for the p38alpha/beta MAPK pathway.

A new bioimaging carrier for fluorescent quantum dots: phospholipid nanoemulsion mimicking natural lipoprotein core.

Fluorescent quantum dots (semiconductor nanocrystals) have the potential to revolutionize biological imaging, but their use has been limited by difficulties in obtaining quantum dots that are water soluble and biocompatible. The objectives of our research were to develop a methodology for encapsulation of cadnium-selenium (CdSe) quantum dots (QDs) in phospholipid nanoemulsion that mimics the natural lipoprotein core and to study their interactions with cultured non-small cell lung cancer cells (NSCLC). We found that CdSe QDs can be efficiently encapsulated in the phospholipid nanoemulsion.

JNK-interacting leucine zipper protein is a novel scaffolding protein in the Galpha13 signaling pathway.

Scaffolding proteins play a critical role in conferring specificity and fidelity to signaling pathways. The JNK-interacting leucine zipper protein (JLP) has been identified as a scaffolding protein involved in linking components of the JNK signaling module. Galpha(12) and Galpha(13), the alpha-subunits of heterotrimeric G proteins G12 and G13, respectively, stimulate the JNK module in diverse cell types.

JLP associates with kinesin light chain 1 through a novel leucine zipper-like domain.

Scaffolding proteins exist in eukaryotes to properly assemble signaling proteins into specific multimeric functional complexes. JLP is a novel leucine zipper protein belonging to a family of scaffolding proteins that assemble JNK signaling modules. JLP is a proline-rich protein that contains two leucine zipper domains and a highly conserved C-terminal domain.

Molecular mechanisms associated with the regulation of apoptosis by the two alternatively spliced products of c-Myb.

The c-myb proto-oncogene encodes two alternatively spliced mRNAs, which in turn code for proteins of 75 kDa and 89 kDa. It is at present unclear whether the two isoforms of c-Myb perform identical functions or whether they mediate different biological effects. To assess their role in apoptotic death of hematopoietic cells, we expressed the two isoforms of c-Myb in the murine myeloid cell lines 32Dcl3 and FDCP1.

c-Myc is essential but not sufficient for c-Myb-mediated block of granulocytic differentiation.

The c-myb proto-oncogene plays a central role in hematopoiesis and encodes a major translational product of 75 kDa. c-Myb is highly expressed in immature hematopoietic cells, and its expression is down-regulated during terminal differentiation. Deregulated expression of c-Myb has been shown to block terminal differentiation of hematopoietic cells.

JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors.

Extracellular signals are transduced into cells through mitogen-activated protein kinases (MAPKs), which are activated by their upstream kinases. Recently, families of scaffolding proteins have been identified to tether specific combinations of these kinases along specific signaling pathways. Here we describe a protein, JLP (c-Jun NH2-terminal kinase-associated leucine zipper protein), which acts as a scaffolding protein to bring together Max and c-Myc along with JNK (c-Jun NH2-terminal kinase) and p38MAPK, as well as their upstream kinases MKK4 (MAPK kinase 4) and MEKK3 (MAPK kinase kinase 3).