scholarly journals Nucleocytoplasmic Trafficking of the Syk Protein Tyrosine Kinase

2006 ◽  
Vol 26 (9) ◽  
pp. 3478-3491 ◽  
Author(s):  
Fei Zhou ◽  
Jianjie Hu ◽  
Haiyan Ma ◽  
Marietta L. Harrison ◽  
Robert L. Geahlen
Keyword(s):  
Oxidative Stress ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Protein Tyrosine Kinase ◽  
Caspase 3 ◽  
Catalytic Domain ◽  
Cell Receptor ◽  
Nucleocytoplasmic Trafficking ◽  
Protein Tyrosine ◽  
Syk Protein Tyrosine Kinase

ABSTRACT The protein tyrosine kinase Syk couples the B-cell receptor (BCR) for antigen to multiple intracellular signaling pathways and also modulates cellular responses to inducers of oxidative stress in a receptor-independent fashion. In B cells, Syk is found in both the nuclear and cytoplasmic compartments but contains no recognizable nuclear localization or export signals. Through the analysis of a series of deletion mutants, we identified the presence of an unconventional shuttling sequence near the junction of the catalytic domain and the linker B region that accounts for Syk's subcellular localization. This localization is altered following prolonged engagement of the BCR, which causes Syk to be excluded from the nucleus. Nuclear exclusion requires the receptor-mediated activation of protein kinase C and new protein synthesis. Both of these processes also potentiate the activation of caspase 3 in cells in response to oxidative stress in a manner that is dependent on the localization of Syk outside of the nucleus. In contrast, restriction of Syk to the nucleus greatly diminishes the stress-induced activation of caspase 3.

The GPI-anchored adhesion molecule F3 induces tyrosine phosphorylation: involvement of the FNIII repeats

1996 ◽  
Vol 109 (3) ◽  
pp. 699-704 ◽  
Author(s):  
M. Cervello ◽  
V. Matranga ◽  
P. Durbec ◽  
G. Rougon ◽  
S. Gomez
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Cho Cells ◽  
Intracellular Signaling ◽  
Protein Tyrosine Kinase ◽  
Cross Linking ◽  
Protein Tyrosine ◽  
Intracellular Signaling Pathway ◽  
Type Iii ◽  
Cell Cell

The glycosyl-phosphatidylinositol (GPI)-anchored F3 molecule, a member of the Ig superfamily made up of Ig and FNIII-like domains, is involved in cell-cell adhesion, neuronal pathfinding and fasciculation. Little is known about the mechanism(s) that governs the F3-mediated cell-cell recognition. In particular, it is not known whether F3 transduces signals across the membrane. Here we show that in F3-transfected CHO cells (1A cells) an increase in tyrosine phosphorylation occurs during F3-mediated aggregation. Moreover, under aggregation conditions F3 immunoprecipitated from 32P-metabolically labeled 1A cells associated with three major phosphorylated proteins. Interestingly, genistein inhibited the F3-mediated aggregation. Increased tyrosine phosphorylation was also observed using antibody-mediated F3-cross-linking. Furthermore, F3 expressed both in 1A cells and in post-natal mouse cerebellum forms non-covalent soluble complexes with protein tyrosine kinase(s). In cerebellum the F3-associated kinase was identified as fyn. By contrast, a truncated F3 protein, expressed in CHO cells, from which all the FN type III repeats have been deleted, does not associate with a kinase. Cross-linking of the F3-truncated form does not induce modulation of tyrosine phosphorylation. Taken together these data demonstrate that F3 is a molecule that transduces signals through both association with protein tyrosine kinase and modulation of protein tyrosine phosphorylation. The presence of FN type III domains is essential for the activation of the intracellular signaling pathway.

Characterization of elk, a brain-specific receptor tyrosine kinase

1991 ◽  
Vol 11 (5) ◽  
pp. 2496-2502
Author(s):  
V Lhoták ◽  
P Greer ◽  
K Letwin ◽  
T Pawson
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Catalytic Domain ◽  
Signal Sequence ◽  
Tyrosine Kinase Domain ◽  
Rat Tissues ◽  
Protein Tyrosine

The elk gene encodes a novel receptorlike protein-tyrosine kinase, which belongs to the eph subfamily. We have previously identified a partial cDNA encompassing the elk catalytic domain (K. Letwin, S.-P. Yee, and T. Pawson, Oncogene 3:621-678, 1988). Using this cDNA as a probe, we have isolated cDNAs spanning the entire rat elk coding sequence. The predicted Elk protein contains all the hallmarks of a receptor tyrosine kinase, including an N-terminal signal sequence, a cysteine-rich extracellular domain, a membrane-spanning segment, a cytoplasmic tyrosine kinase domain, and a C-terminal tail. In both amino acid sequence and overall structure, Elk is most similar to the Eph and Eck protein-tyrosine kinases, suggesting that the eph, elk, and eck genes encode members of a new subfamily of receptorlike tyrosine kinases. Among rat tissues, elk expression appears restricted to brain and testes, with the brain having higher levels of both elk RNA and protein. Elk protein immunoprecipitated from a rat brain lysate becomes phosphorylated on tyrosine in an in vitro kinase reaction, consistent with the prediction that the mammalian elk gene encodes a tyrosine kinase capable of autophosphorylation. The characteristics of the Elk tyrosine kinase suggest that it may be involved in cell-cell interactions in the nervous system.

Oxidative stress-induced cell death of human oral neutrophils

2003 ◽  
Vol 284 (4) ◽  
pp. C1048-C1053 ◽  
Author(s):  
Eisuke F. Sato ◽  
Masahiro Higashino ◽  
Kazuo Ikeda ◽  
Ryotaro Wake ◽  
Mitsuyoshi Matsuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Caspase 3 ◽  
Nuclear Dna ◽  
Kinase Inhibitor ◽  
Tissue Injury ◽  
Morphological Changes ◽  
Limited Information ◽  
And Function

Polymorphonuclear leukocytes (PMN) play crucial roles in protecting hosts against invading microbes and in the pathogenesis of inflammatory tissue injury. Although PMN migrate into mucosal layers of digestive and respiratory tracts, only limited information is available of their fate and function in situ. We previously reported that, unlike circulating PMN (CPMN), PMN in the oral cavity spontaneously generate superoxide radical and nitric oxide (NO) in the absence of any stimuli. When cultured for 12 h under physiological conditions, oral PMN (OPMN) showed morphological changes that are characteristic of those of apoptosis. Upon agarose gel electrophoresis, nuclear DNA samples isolated from OPMN revealed ladder-like profiles characteristic of nucleosomal fragmentation.l-cysteine, reduced glutathione (GSH), and herbimycin A, a protein tyrosine kinase inhibitor, suppressed the activation of caspase-3 and apoptosis of OPMN. Neither thiourea, superoxide dismutase (SOD), nor catalase inhibited the activation of caspase-3 and apoptosis. Moreover, N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), inhibitor for caspase-3, inhibited the fragmentation of DNA. These results suggested that oxidative stress and/or tyrosine-kinase-dependent pathway(s) activated caspase-3 in OPMN, thereby inducing their apoptosis.

scholarly journals Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor

Nature ◽  
2007 ◽  
Vol 446 (7137) ◽  
pp. 824-824
Author(s):  
Marcos H. Hatada ◽  
Xiaode Lu ◽  
Ellen R. Laird ◽  
Jeremy Green ◽  
Jay P. Morgenstern ◽  
...  
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
Molecular Basis ◽  
Protein Tyrosine Kinase ◽  
Cell Receptor ◽  
Protein Tyrosine

Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn)

Cell ◽  
1991 ◽  
Vol 65 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Michael P. Cooke ◽  
Kristin M. Abraham ◽  
Katherine A. Forbush ◽  
Roger M. Perimutter
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
Protein Tyrosine Kinase ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
Protein Tyrosine ◽  
Family Protein ◽  
T Cell Receptor Signaling ◽  
Cell Receptor Signaling

Bradykinin- and substance P-induced edema formation in the hamster cheek pouch is tyrosine kinase dependent

2007 ◽  
Vol 103 (1) ◽  
pp. 184-189 ◽  
Author(s):  
Israel Rubinstein
Keyword(s):  
Substance P ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Protein Tyrosine Kinase ◽  
Cell Function ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Endothelial Cell Function ◽  
Protein Tyrosine

The purpose of this study was to determine whether protein tyrosine kinase, a ubiquitous family of intracellular signaling enzymes that regulates endothelial cell function, modulates bradykinin- and substance P-induced increase in macromolecular efflux from the intact hamster cheek pouch microcirculation. Using intravital microscopy, I found that suffusion of bradykinin or substance P (each, 0.5 and 1.0 μM) onto the cheek pouch elicited significant, concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (FITC-dextran; molecular mass, 70 kDa; P < 0.05). These responses were significantly attenuated by suffusion of genistein (1.0 μM) or tyrphostin 25 (10 μM), two structurally unrelated, nonspecific protein tyrosine kinase inhibitors ( P < 0.05). Conceivably, the kinase(s) involved in this process could be agonist specific because genistein was more effective than tyrphostin 25 in attenuating bradykinin-induced responses while the opposite was observed with substance P. Both inhibitors had no significant effects on adenosine (0.5 M)-induced responses ( P > 0.5). Collectively, these data suggest that the protein tyrosine kinase metabolic pathway modulates, in part, the edemagenic effects of bradykinin and substance P in the intact hamster cheek pouch microcirculation in a specific fashion.

scholarly journals ZAP-70 Association with T Cell Receptor ζ (TCRζ): Fluorescence Imaging of Dynamic Changes upon Cellular Stimulation

1998 ◽  
Vol 143 (3) ◽  
pp. 613-624 ◽  
Author(s):  
Joanne Sloan-Lancaster ◽  
John Presley ◽  
Jan Ellenberg ◽  
Tetsuo Yamazaki ◽  
Jennifer Lippincott-Schwartz ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
Protein Tyrosine Kinase ◽  
Specific Interaction ◽  
Active Form ◽  
Lymphocyte Activation ◽  
Cell Receptor ◽  
Protein Tyrosine

The nonreceptor protein tyrosine kinase ZAP-70 is a critical enzyme required for successful T lymphocyte activation. After antigenic stimulation, ZAP-70 rapidly associates with T cell receptor (TCR) subunits. The kinetics of its translocation to the cell surface, the properties of its specific interaction with the TCRζ chain expressed as a chimeric protein (TTζ and Tζζ), and its mobility in different intracellular compartments were studied in individual live HeLa cells, using ZAP-70 and Tζζ fused to green fluorescent protein (ZAP-70 GFP and Tζζ–GFP, respectively). Time-lapse imaging using confocal microscopy indicated that the activation-induced redistribution of ZAP-70 to the plasma membrane, after a delayed onset, is of long duration. The presence of the TCRζ chain is critical for the redistribution, which is enhanced when an active form of the protein tyrosine kinase Lck is coexpressed. Binding specificity to TTζ was indicated using mutant ZAP-70 GFPs and a truncated ζ chimera. Photobleaching techniques revealed that ZAP-70 GFP has decreased mobility at the plasma membrane, in contrast to its rapid mobility in the cytosol and nucleus. Tζζ– GFP is relatively immobile, while peripherally located ZAP-70 in stimulated cells is less mobile than cytosolic ZAP-70 in unstimulated cells, a phenotype confirmed by determining the respective diffusion constants. Examination of the specific molecular association of signaling proteins using these approaches has provided new insights into the TCRζ–ZAP-70 interaction and will be a powerful tool for continuing studies of lymphocyte activation.

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