scholarly journals Are Src family kinases involved in cell cycle resumption in rat eggs?

Reproduction ◽  
2004 ◽  
Vol 127 (4) ◽  
pp. 455-463 ◽  
Author(s):  
A Talmor-Cohen ◽  
R Tomashov-Matar ◽  
E Eliyahu ◽  
R Shapiro ◽  
R Shalgi
Keyword(s):  
Signal Transduction ◽  
Marine Invertebrate ◽  
Src Family Kinases ◽  
Egg Activation ◽  
Signal Transduction Pathways ◽  
Cortical Granules ◽  
Fusion Site ◽  
Intracellular Ca ◽  
Intensive Investigation ◽  
Mammalian Eggs

The earliest visible indications for the transition to embryos in mammalian eggs, known as egg activation, are cortical granules exocytosis (CGE) and resumption of meiosis (RM); these events are triggered by the fertilizing spermatozoon through a series of Ca2+transients. The pathways, within the egg, leading to the intracellular Ca2+release and to the downstream cellular events, are currently under intensive investigation. The involvement of Src family kinases (SFKs) in Ca2+release at fertilization is well supported in marine invertebrate eggs but not in mammalian eggs. In a previous study we have shown the expression and localization of Fyn, the first SFK member demonstrated in the mammalian egg. The purpose of the current study was to identify other common SFKs and resolve their function during activation of mammalian eggs. All three kinases examined: Fyn, c-Src and c-Yes are distributed throughout the egg cytoplasm. However, Fyn and c-Yes tend to concentrate at the egg cortex, though only Fyn is localized to the spindle as well. The different localizations of the various SFKs imply the possibility of their different functions within the egg. To examine whether SFKs participate in the signal transduction pathways during egg activation, we employed selective inhibitors of the SFKs activity ((PP2 and SU6656). The results demonstrate that RM, which is triggered by Ca2+elevation, is an SFK-dependent process, while CGE, triggered by either Ca2+elevation or protein kinase C (PKC), is not. The possible involvement of SFKs in the signal transduction pathways that lead from the sperm–egg fusion site downstream of the Ca2+release remains unclear.

Signal transduction pathways involved in fluid flow-induced PGE2 production by cultured osteocytes

1999 ◽  
Vol 276 (1) ◽  
pp. E171-E178 ◽  
Author(s):  
N. E. Ajubi ◽  
J. Klein-Nulend ◽  
M. J. Alblas ◽  
E. H. Burger ◽  
P. J. Nijweide
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Fluid Flow ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Phospholipase A ◽  
Signal Transduction Pathways ◽  
Prostaglandin E ◽  
Kinase C ◽  
Intracellular Ca

To maintain its structural competence, the skeleton adapts to changes in its mechanical environment. Osteocytes are generally considered the bone mechanosensory cells that translate mechanical signals into biochemical, bone metabolism-regulating stimuli necessary for the adaptive process. Prostaglandins are an important part of this mechanobiochemical signaling. We investigated the signal transduction pathways in osteocytes through which mechanical stress generates an acute release of prostaglandin E2(PGE2). Isolated chicken osteocytes were subjected to 10 min of pulsating fluid flow (PFF; 0.7 ± 0.03 Pa at 5 Hz), and PGE2release was measured. Blockers of Ca2+ entry into the cell or Ca2+ release from internal stores markedly inhibited the PFF-induced PGE2 release, as did disruption of the actin cytoskeleton by cytochalasin B. Specific inhibitors of Ca2+-activated phospholipase C, protein kinase C, and phospholipase A2 also decreased PFF-induced PGE2 release. These results are consistent with the hypothesis that PFF raises intracellular Ca2+ by an enhanced entry through mechanosensitive ion channels in combination with Ca2+- and inositol trisphosphate (the product of phospholipase C)-induced Ca2+ release from intracellular stores. Ca2+ and protein kinase C then stimulate phospholipase A2activity, arachidonic acid production, and ultimately PGE2 release.

Differential effects of β-arrestins on the internalization, desensitization and ERK1/2 activation downstream of protease activated receptor-2

2007 ◽  
Vol 293 (1) ◽  
pp. C346-C357 ◽  
Author(s):  
P. Kumar ◽  
C. S. Lau ◽  
M. Mathur ◽  
P. Wang ◽  
K. A. DeFea
Keyword(s):  
Signal Transduction ◽  
Membrane Receptors ◽  
Receptor Internalization ◽  
Signal Transduction Pathways ◽  
Receptor Desensitization ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Functional Roles ◽  
Intracellular Ca ◽  
Protease Activated Receptor 2

β-Arrestins-1 and 2 are known to play important roles in desensitization of membrane receptors and facilitation of signal transduction pathways. It has been previously shown that β-arrestins are required for signal termination, internalization, and ERK1/2 activation downstream of protease-activated-receptor-2 (PAR-2), but it is unclear whether they are functionally redundant or mediate specific events. Here, we demonstrate that in mouse embryonic fibroblasts (MEFs) from β-arrestin-1/2 knockout mice, Gαq signaling by PAR-2, as measured by mobilization of intracellular Ca2+, is prolonged. Only expression of β-arrestin-1 shortened the signal duration, whereas either β-arrestin-1 or 2 was able to restore PKC-induced receptor desensitization. β-arrestin-1 also mediated early, while β-arrestin-2 mediated delayed, receptor internalization and membrane-associated ERK1/2 activation. While β-arrestin-1 colocalized with a lysosomal marker (LAMP-1), β-arrestin-2 did not, suggesting a specific role for β-arrestin-1 in lysosomal receptor degradation. Together, these data suggest distinct temporal and functional roles for β-arrestins in PAR-2 signaling, desensitization, and internalization.

scholarly journals Drosophila C-Terminal Src Kinase Negatively Regulates Organ Growth and Cell Proliferation through Inhibition of the Src, Jun N-Terminal Kinase, and STAT Pathways

2004 ◽  
Vol 24 (15) ◽  
pp. 6676-6689 ◽  
Author(s):  
Renee D. Read ◽  
Erika A. Bach ◽  
Ross L. Cagan
Keyword(s):  
Signal Transduction ◽  
Cellular Proliferation ◽  
Src Kinase ◽  
Src Family Kinases ◽  
Negative Regulator ◽  
Signal Transduction Pathways ◽  
Organ Growth ◽  
Cellular Processes ◽  
Jun Kinase

ABSTRACT Src family kinases regulate multiple cellular processes including proliferation and oncogenesis. C-terminal Src kinase (Csk) encodes a critical negative regulator of Src family kinases. We demonstrate that the Drosophila melanogaster Csk ortholog, dCsk, functions as a tumor suppressor: dCsk mutants display organ overgrowth and excess cellular proliferation. Genetic analysis indicates that the dCsk−/− overgrowth phenotype results from activation of Src, Jun kinase, and STAT signal transduction pathways. In particular, blockade of STAT function in dCsk mutants severely reduced Src-dependent overgrowth and activated apoptosis of mutant tissue. Our data provide in vivo evidence that Src activity requires JNK and STAT function.

scholarly journals SU6656, a Selective Src Family Kinase Inhibitor, Used To Probe Growth Factor Signaling

2000 ◽  
Vol 20 (23) ◽  
pp. 9018-9027 ◽  
Author(s):  
Robert A. Blake ◽  
Martin A. Broome ◽  
Xiangdong Liu ◽  
Jianming Wu ◽  
Mikhail Gishizky ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Small Molecule ◽  
Sh2 Domain ◽  
Src Family Kinases ◽  
Dominant Negative ◽  
Signal Transduction Pathways ◽  
Pdgf Receptor ◽  
Additional Tool

ABSTRACT The use of small-molecule inhibitors to study molecular components of cellular signal transduction pathways provides a means of analysis complementary to currently used techniques, such as antisense, dominant-negative (interfering) mutants and constitutively activated mutants. We have identified and characterized a small-molecule inhibitor, SU6656, which exhibits selectivity for Src and other members of the Src family. A related inhibitor, SU6657, inhibits many kinases, including Src and the platelet-derived growth factor (PDGF) receptor. The use of SU6656 confirmed our previous findings that Src family kinases are required for both Myc induction and DNA synthesis in response to PDGF stimulation of NIH 3T3 fibroblasts. By comparing PDGF-stimulated tyrosine phosphorylation events in untreated and SU6656-treated cells, we found that some substrates (for example, c-Cbl, and protein kinase C δ) were Src family substrates whereas others (for example, phospholipase C-γ) were not. One protein, the adaptor Shc, was a substrate for both Src family kinases (on tyrosines 239 and 240) and a distinct tyrosine kinase (on tyrosine 317, which is perhaps phosphorylated by the PDGF receptor itself). Microinjection experiments demonstrated that a Shc molecule carrying mutations of tyrosines 239 and 240, in conjunction with an SH2 domain mutation, interfered with PDGF-stimulated DNA synthesis. Deletion of the phosphotyrosine-binding domain also inhibited synthesis. These inhibitions were overcome by heterologous expression of Myc, supporting the hypothesis that Shc functions in the Src pathway. SU6656 should prove a useful additional tool for further dissecting the role of Src kinases in this and other signal transduction pathways.

Signal-regulated oxidation of proteins via MICAL

2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert
Keyword(s):  
Signal Transduction ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Redox Regulation ◽  
Signal Transduction Pathways ◽  
Cellular Functions ◽  
Intracellular Signals ◽  
Amino Acid Side Chains ◽  
Specific Receptors ◽  
Sulfur Containing

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.

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