scholarly journals Involvement of Src in the Adaptation of Cancer Cells under Microenvironmental Stresses

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
A. K. M. Mahbub Hasan ◽  
Takashi Ijiri ◽  
Ken-ichi Sato
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Protein Tyrosine Phosphorylation ◽  
Cellular Functions ◽  
Specific Behavior ◽  
Protein Tyrosine ◽  
Health And Disease ◽  
The Relationship

Protein-tyrosine phosphorylation, which is catalyzed by protein-tyrosine kinase (PTK), plays a pivotal role in a variety of cellular functions related to health and disease. The discovery of the viral oncogene Src (v-Src) and its cellular nontransforming counterpart (c-Src), as the first example of PTK, has opened a window to study the relationship between protein-tyrosine phosphorylation and the biology and medicine of cancer. In this paper, we focus on the roles played by Src and other PTKs in cancer cell-specific behavior, that is, evasion of apoptosis or cell death under stressful extracellular and/or intracellular microenvironments (i.e., hypoxia, anoikis, hypoglycemia, and serum deprivation).

Regulation of intestinal tyrosine phosphorylation and programmed cell death by peroxovanadate

1999 ◽  
Vol 277 (3) ◽  
pp. C572-C579 ◽  
Author(s):  
Lawrence A. Scheving ◽  
Jiji R. Thomas ◽  
Linda Zhang
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Programmed Cell Death ◽  
Tyrosine Phosphorylation ◽  
Intestinal Epithelial Cell ◽  
Tyrosine Phosphatase ◽  
Active Form ◽  
Intestinal Epithelial ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine

Cell suspensions of ileal mucosa undergo a rapid and synchronized form of programmed cell death when cultured in a simple medium at 37°C. Because tyrosine phosphorylation of proteins plays a crucial role in the signal transduction of many cellular processes, we examined its role in intestinal programmed cell death by use of immunoblot and immunohistochemical methods. We observed a 50–70% reduction in tyrosine phosphorylation during the initial 10 min of intestinal epithelial cell culture. We hypothesized that the inhibition of protein tyrosine phosphatases would increase protein tyrosine phosphorylation in these suspensions and decrease programmed cell death. A strong inhibitor of these phosphatases (peroxovanadate) but not a weaker one (sodium orthovanadate) abolished the DNA fragmentation/laddering normally seen in dying enterocytes. Peroxovanadate enhanced protein tyrosine phosphorylation of many intestinal proteins, dramatically increasing the dually phosphorylated and active form of mitogen-activated protein kinase. Immunohistochemistry revealed a particularly high level of increased tyrosine phosphorylation in the intestinal crypts in peroxovanadate-treated mucosa. Kinetic studies indicated that the pivotal time for protein tyrosine phosphatase inhibition occurred within 5 min of ex vivo culture, precisely when protein tyrosine phosphorylation declined. Our data suggest that tyrosine kinase inactivation or tyrosine phosphatase activation may initiate intestinal epithelial cell death.

scholarly journals Beta 2 integrin-dependent protein tyrosine phosphorylation and activation of the FGR protein tyrosine kinase in human neutrophils.

1994 ◽  
Vol 126 (4) ◽  
pp. 1111-1121 ◽  
Author(s):  
G Berton ◽  
L Fumagalli ◽  
C Laudanna ◽  
C Sorio
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Class I ◽  
Human Neutrophils ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Mhc Antigens ◽  
Beta 2

Stimulation of adherent human neutrophils (PMN) with tumor necrosis factor (TNF) triggers protein tyrosine phosphorylation (Fuortes, M., W. W. Jin, and C. Nathan. 1993. J. Cell Biol. 120:777-784). We investigated the dependence of this response on beta 2 integrins by using PMN isolated from a leukocyte adhesion deficiency (LAD) patient, which do not express beta 2 integrins, and by plating PMN on surface bound anti-beta 2 (CD18) antibodies. Protein tyrosine phosphorylation increased in PMN plated on fibrinogen and this phosphorylation was enhanced by TNF. Triggering of protein tyrosine phosphorylation did not occur in LAD PMN plated on fibrinogen either in the absence or the presence of TNF. Surface bound anti-CD18, but not isotype-matched anti-Class I major histocompatibility complex (MHC) antigens, antibodies triggered tyrosine phosphorylation in normal, but not in LAD PMN. As the major tyrosine phosphorylated proteins we found in our assay conditions migrated with an apparent molecular mass of 56-60 kD, we investigated whether beta 2 integrins are implicated in activation of members of the src family of intracellular protein-tyrosine kinases. We found that the fgr protein-tyrosine kinase (p58fgr) activity, and its extent of phosphorylation in tyrosine, in PMN adherent to fibrinogen, was enhanced by TNF. Activation of p58fgr in response to TNF was evident within 10 min of treatment and increased with times up to 30 min. Also other activators of beta 2 integrins such as phorbol-12-myristate 13-acetate (PMA), and formyl methionyl-leucyl-phenylalanine (FMLP), induced activation of p58fgr kinase activity. Activation of p58fgr kinase activity, and phosphorylation in tyrosine, did not occur in PMN of a LAD patient in response to TNF. Soluble anti-CD18, but not anti-Class I MHC antigens, antibodies inhibited activation of p58fgr kinase activity in PMN adherent to fibrinogen in response to TNF, PMA, and FMLP. These findings demonstrate that, in PMN, beta 2 integrins are implicated in triggering of protein tyrosine phosphorylation, and establish a link between beta 2 integrin-dependent adhesion and the protein tyrosine kinase fgr in cell signaling.

Inhibition by 5′-methylthioadenosine of cell growth and tyrosine kinase activity stimulated by fibroblast growth factor receptor in human gliomas

1995 ◽  
Vol 83 (4) ◽  
pp. 690-697 ◽  
Author(s):  
Katsuya Miyaji ◽  
Eiichi Tani ◽  
Atsuhisa Nakano ◽  
Hideyasu Ikemoto ◽  
Keizo Kaba
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Glioma Cells ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Kinase Activity ◽  
Protein Tyrosine

✓ Stimulation of three human glioma cell lines with basic fibroblast growth factor (bFGF) led to the enhancement of cell growth and the rapid tyrosine phosphorylation of cellular proteins, including major substrates of 90 kD. A methyltransferase inhibitor, 5′-methylthioadenosine (MTA), inhibited dose dependently the bFGF-stimulated cell growth and protein tyrosine phosphorylation in glioma cells by blocking both receptor autophosphorylation and substrate phosphorylation, as shown by immunoblotting with antiphosphotyrosine antibodies and cross-linking bFGF to receptors. The antiproliferative activity of MTA correlated quantitatively with its potency as an inhibitor of bFGF-stimulated protein tyrosine kinase activity. The methyltransferase inhibitor MTA had no effect on either epidermal growth factor— or platelet-derived growth factor—stimulated protein tyrosine phosphorylation in glioma cells, but inhibited specifically bFGF-stimulated protein tyrosine kinase activity. The concentration of MTA required for inhibition of protein methylation correlated well with the concentration required for inhibition of bFGF-stimulated cell growth and protein tyrosine phosphorylation. Because MTA had no effect on numbers and dissociation constants of high- and low-affinity bFGF receptors, the inhibition of bFGF-stimulated bFGF receptor tyrosine kinase activity is not likely to be the result of a reduction in bFGF receptor and bFGF binding capacity. In fact, MTA delayed and reduced the internalization and nuclear translocation of bFGF, and the internalized bFGF was submitted to a limited proteolysis that converted it to lower molecular peptides whose presence remained for at least 22 hours. The effect of MTA on bFGF-stimulated tyrosine phosphorylation was immediate and readily reversible.

scholarly journals Tissue-dependent regulation of protein tyrosine kinase activity during embryonic development.

1991 ◽  
Vol 112 (5) ◽  
pp. 955-963 ◽  
Author(s):  
P A Maher
Keyword(s):  
Embryonic Development ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Kinase Activity ◽  
Protein Tyrosine ◽  
Low Levels ◽  
Protein Tyrosine Kinase Activity

Protein tyrosine kinase activity was assayed in a variety of chicken tissues during embryonic development and in the adult. In some tissues protein tyrosine kinase activity decreased during embryonic development; however, in other tissues it remained high throughout development, it contrast to the level of protein tyrosine phosphorylation, which decreased during development. The highest levels of tyrosine kinase activity were detected in 17-d embryonic brain although only low levels of protein tyrosine phosphorylation were observed in this tissue. Several alternatives were examined in an effort to determine the mechanism responsible for the low levels of tyrosine phosphorylated proteins in most older embryonic and adult chicken tissues despite the presence of highly active tyrosine kinases. The results show that the regulation of protein tyrosine phosphorylation during embryonic development is complex and varies from tissue to tissue. Furthermore, the results suggest that protein tyrosine phosphatases play an important role in regulating the level of phosphotyrosine in proteins of many older embryonic and adult tissues.

scholarly journals Cell proliferation status, cytokine action and protein tyrosine phosphorylation modulate leukotriene biosynthesis in a basophil leukaemia and a mastocytoma cell line

1994 ◽  
Vol 299 (2) ◽  
pp. 467-472 ◽  
Author(s):  
W Hagmann
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Interleukin 4 ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Herbimycin A ◽  
Mastocytoma Cells

Mast cells, mastocytoma cells and basophil leukaemia cells are well-established producers of leukotrienes when grown and stimulated appropriately. I report that the cells' ability to produce leukotrienes is dependent on the cells' proliferative status or their provision with growth factors. Proliferating MC/9 and subconfluent RBL2H3 cells respond maximally to stimulation by 1 microM ionomycin with the production of 56 and 32 pmol of cysteinyl-leukotrienes/10(6) cells respectively. In contrast, confluent RBL2H3 or growth-arrested MC/9 cells lose their ability to generate leukotrienes in response to ionomycin treatment. This rapid down-regulation of leukotriene synthesis is also observed when proliferating RBL2H3 cells are transferred to growth-factor-free medium, wherein cellular leukotriene-synthesis capacity has an apparent half-lifetime of 60 min. Transfer back into growth medium results in the regeneration of leukotriene synthesis capacity within 6 h. In growth-arrested MC/9 cells, leukotriene production ability can at least partially be restored by priming the cells with interleukin 3, but not with interleukin 4. In RBL2H3 cells, pretreatment with protein tyrosine kinase inhibitors such as genistein (5 min, 37 microM), herbimycin A (6 h, 3 microM) or tyrphostin 25 (16 h, 100 microM) completely inhibits leukotriene generation, whereas okadaic acid (15 min, 0.5 microM) has no effect. Under these conditions, both genistein and herbimycin A strongly impair ionomycin-induced protein tyrosine phosphorylation. Our study indicates that leukotriene generation in these tumour cells is tightly regulated by their proliferation status and supply with growth factors, and cell stimulation towards leukotriene synthesis appears to involve protein tyrosine kinase activity.

scholarly journals Effect of genistein addition to equine sperm freezing extender

2018 ◽  
Vol 66 (4) ◽  
pp. 241 ◽  
Author(s):  
Β. MACÍAS-GARCÍA ◽  
Τ. GUIMARÃES ◽  
G. LOPES ◽  
A. ROCHA ◽  
L. GONZÁLEZ-FERNÁNDEZ
Keyword(s):  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Sperm Quality ◽  
Protein Tyrosine Phosphorylation ◽  
Sperm Viability ◽  
Protein Tyrosine ◽  
Progressive Motility ◽  
Ros Scavenger

Cryopreservation negatively affects equine sperm quality post-thaw: an excessive release of reactive oxygen species (ROS) and increased protein tyrosine phosphorylation (known as cryocapacitation) have been demonstrated in frozenthawed equine sperm diminishing its lifespan. The objective of this study was to determine the possible beneficial effect of genistein addition (a ROS scavenger and protein tyrosine kinase inhibitor) to a commercial freezing extender. Equine sperm were frozen in the presence of different genistein concentrations ranging from 0 to 800 μM. After thawing, the sperm viability (eosinnigrosin), acrosome integrity using peanut agglutinin (PNA), protein tyrosine phosphorylation (PY) and motility were assessed at times 0 and 1 hr. In addition PY was studied in fresh and frozen sperm incubated in Modified Whitten’s (MW) medium with 25 mM Bicarbonate (MW+Bic). Genistein did not affect the viability, total or progressive motility or acrosome status of frozenthawed equine sperm. Immediately after thawing, positive PY staining in the equatorial band was observed and genistein addition did not exert any change in PY. Fresh sperm incubated in MW+Bic showed a significant increase in PY staining along the tail compared to frozen-thawed sperm. In our study sperm viability immediately post-thaw was 58.25% ± 5.35 and progressive motility 14.46% ± 5.7 (mean ± S.E.M.) and genistein did not improve the post-thaw quality of equine sperm. In addition, cryopreservation did not induce PY immediately post-thaw or enhanced frozen-thawed equine sperm susceptibility to PY induction.

scholarly journals Specific tyrosine phosphorylation induced in Schistosoma mansoni miracidia by haemolymph from schistosome susceptible, but not resistant, Biomphalaria glabrata

Parasitology ◽  
2007 ◽  
Vol 135 (3) ◽  
pp. 337-345 ◽  
Author(s):  
A. J. WALKER ◽  
D. ROLLINSON
Keyword(s):  
Tyrosine Kinase ◽  
Schistosoma Mansoni ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Fold Increase ◽  
Biomphalaria Glabrata ◽  
Snail Host ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine

SUMMARYMolecular interplay during snail-schistosome interactions is poorly understood and there is much to discover concerning the effect of snail host molecules on molecular processes in schistosomes. Using the Biomphalaria glabrata – Schistosoma mansoni host-parasite system, the effects of exposure to haemolymph, derived from schistosome-resistant and susceptible snail strains, on protein tyrosine phosphorylation in miracidia have been investigated. Western blotting revealed several tyrosine phosphorylated proteins in this larval stage. Exposure of miracidia to haemolymph from susceptible snails for 60 min resulted in a striking, 5-fold, increase in the tyrosine phosphorylation of a 56 kDa (p56) S. mansoni protein. In contrast, haemolymph from resistant snails had little effect on protein tyrosine phosphorylation levels in miracidia. Confocal microscopy revealed that tyrosine phosphorylation was predominantly associated with proteins present in the tegument. Finally, treatment of miracidia with the tyrosine kinase inhibitor genistein significantly impaired their development into primary sporocysts. The results open avenues for research that focus on the potential importance of phospho-p56 to the outcome of schistosome infection in snails, and the significance of protein tyrosine kinase-mediated signalling events to the transformation of S. mansoni larvae.

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