scholarly journals Signalling in Neutrophils: A Retro Look

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Paul H. Naccache
Keyword(s):  
Tyrosine Kinases ◽  
Second Messengers ◽  
Biological Properties ◽  
Present Knowledge ◽  
Polymorphonuclear Neutrophils ◽  
Signalling Pathways ◽  
Surface Receptors ◽  
The Core ◽  
Kinase C ◽  
Functional Responsiveness

This review presents a summary of signalling events related to the activation of human polymorphonuclear neutrophils by a variety of soluble and particulate agonists. It is not intended as a comprehensive review of this vast field or as a presentation of the multiple new aspects of neutrophil functions that are being documented at an ever faster rate. Its aim is rather to focus on multiple aspects of major signalling pathways that, in the view of this reviewer, are currently shadowed by present trends and to provide the core evidence for their implication and the limitations of our present knowledge. More specifically, this review starts with cell surface receptors and some of their functional and biological properties and then moves on to downstream transducers (G proteins) and effectors (the phosphoinositide, tyrosine kinases, and cyclic nucleotide pathways). Classical second messengers (calcium, protein kinase C, polyphosphoinositides, and cyclic nucleotides) are emphasized. It is hoped that this presentation will not only remind present-day investigators of the central role these pathways play in the regulation of the functional responsiveness of neutrophils, but that it will also highlight some of the areas deserving additional investigation.

Oncogenes, ions, and phospholipids

1985 ◽  
Vol 248 (1) ◽  
pp. C3-C11 ◽  
Author(s):  
I. G. Macara
Keyword(s):  
Cell Proliferation ◽  
Tyrosine Kinases ◽  
Phorbol Esters ◽  
Second Messengers ◽  
Future Research ◽  
Lipid Biochemistry ◽  
Cytosolic Ph ◽  
Pi Turnover ◽  
Transport Studies ◽  
Kinase C

Recent discoveries in tumor virology, lipid biochemistry, and ion transport studies promise to revolutionize our understanding of cell proliferation, differentiation, and tumorigenesis. A model is proposed, based on similar schemes presented recently by others, that incorporates these discoveries and provides a focus for future research on the functions of oncogene proteins. The model suggests that the early (competence) events in the initiation of cell proliferation are triggered by activation of phosphatidylinositol (PI) turnover, which releases two second messengers, 1,2-diacylglycerol (1,2-DG) and inositol-1,4,5-trisphosphate (IP3). PI turnover is proposed to be regulated by the oncogene protein kinases (src, ros, abl, fps) either directly (acting as PI kinases) or indirectly (as tyrosine kinases). The IP3 triggers Ca2+ release from internal stores, and the elevation of cytosolic Ca2+ acts synergistically with 1,2-DG to activate the Ca2+- and phospholipid-dependent kinase C. Kinase C copurifies with the receptor for the tumor-promoting phorbol esters. It is suggested that kinase C then activates the Na+-H+ exchange system, resulting in an elevation of cytosolic pH and Na+, and that these ionic signals (including the change in Ca2+), either in concert or individually, induce further events, including expression of the protooncogene c-myc, which together commit the cell to initiate replication. Evidences in support of this model are reviewed, together with complications indicating its present inadequacies, particularly recent data suggesting that 1,2-DG may activate tyrosine kinases independent of kinase C.

scholarly journals Deviating from the Beaten Track: New Twists in Brassinosteroid Receptor Function

2020 ◽  
Vol 21 (5) ◽  
pp. 1561 ◽  
Author(s):  
Sebastian Wolf
Keyword(s):  
Conceptual Models ◽  
Signalling Pathways ◽  
Environmental Cues ◽  
Receptor Complex ◽  
Environmental Signals ◽  
Surface Receptors ◽  
The Core ◽  
Beaten Track ◽  
Multiple Levels ◽  
New Evidence

A key feature of plants is their plastic development tailored to the environmental conditions. To integrate environmental signals with genetic growth regulatory programs, plants rely on a number of hormonal pathways, which are intimately connected at multiple levels. Brassinosteroids (BRs), a class of plant sterol hormones, are perceived by cell surface receptors and trigger responses instrumental in tailoring developmental programs to environmental cues. Arguably, BR signalling is one of the best-characterized plant signalling pathways, and the molecular composition of the core signal transduction cascade seems clear. However, BR research continues to reveal new twists to re-shape our view on this key signalling circuit. Here, exciting novel findings pointing to the plasma membrane as a key site for BR signalling modulation and integration with other pathways are reviewed and new inputs into the BR signalling pathway and emerging “non-canonical” functions of the BR receptor complex are highlighted. Together, this new evidence underscores the complexity of plant signalling integration and serves as a reminder that highly-interconnected signalling pathways frequently comprise non-linear aspects which are difficult to convey in classical conceptual models.

scholarly journals Cellular control of renin secretion

1999 ◽  
Vol 202 (3) ◽  
pp. 219-225
Author(s):  
A. Kurtz ◽  
C. Wagner
Keyword(s):  
Protein Kinase ◽  
Inhibitory Action ◽  
Second Messengers ◽  
Present Knowledge ◽  
Renin Secretion ◽  
Protein Kinase G ◽  
Juxtaglomerular Cells ◽  
Kinase C ◽  
Cl Channels ◽  
Cellular Control

Renin secretion at the level of renal juxtaglomerular cells appears to be controlled mainly by classic second messengers such as Ca2+, cyclic AMP and cyclic GMP, which in turn exert their effects through oppositely acting protein kinases and probably also by affecting the activity of ion channels in the plasma membrane. Thus, protein kinase A stimulates renin secretion, whilst protein kinase C and protein kinase G II inhibit renin secretion. Moreover, Cl- channels could be involved in the mediation of the inhibitory action of Ca2+ on renin secretion. This review summarizes our present knowledge about the possible actions of these kinases in renal juxtaglomerular cells and considers pathways in the organ control of renin secretion.

scholarly journals Ca2+ Microdomains, Calcineurin and the Regulation of Gene Transcription

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Gerald Thiel ◽  
Tobias Schmidt ◽  
Oliver G. Rössler
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Gene Transcription ◽  
Intracellular Signaling ◽  
Second Messengers ◽  
Major Function ◽  
Surface Receptors ◽  
Dependent Protein

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.

Involvement of protein kinase C, tyrosine kinases, and Rho kinase in Ca2+ handling of human small arteries

2000 ◽  
Vol 279 (3) ◽  
pp. H1228-H1238 ◽  
Author(s):  
M. Carmen Martínez ◽  
Voahanginirina Randriamboavonjy ◽  
Patrick Ohlmann ◽  
Narcisse Komas ◽  
Juan Duarte ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Tyrosine Kinases ◽  
Rho Kinase ◽  
Free Medium ◽  
Kinase C ◽  
Intracellular Ca ◽  
Pkc Inhibitors ◽  
Continuous Presence

The mechanisms of Ca2+ handling and sensitization were investigated in human small omental arteries exposed to norepinephrine (NE) and to the thromboxane A2 analog U-46619. Contractions elicited by NE and U-46619 were associated with an increase in intracellular Ca2+ concentration ([Ca2+]i), an increase in Ca2+-independent signaling pathways, or an enhancement of the sensitivity of the myofilaments to Ca2+. The two latter pathways were abolished by protein kinase C (PKC), tyrosine kinase (TK), and Rho-associated protein kinase (ROK) inhibitors. In Ca2+-free medium, both NE and U-46619 elicited an increase in tension that was greatly reduced by PKC inhibitors and abolished by caffeine or ryanodine. After depletion of Ca2+ stores with NE and U-46619 in Ca2+-free medium, addition of CaCl2 in the continuous presence of the agonists produced increases in [Ca2+]i and contractions that were inhibited by nitrendipine and TK inhibitors but not affected by PKC inhibitors. NE and U-46619 induced tyrosine phosphorylation of a 42- or a 58-kDa protein, respectively. These results indicate that the mechanisms leading to contraction elicited by NE and U-46619 in human small omental arteries are composed of Ca2+ release from ryanodine-sensitive stores, Ca2+ influx through nitrendipine-sensitive channels, and Ca2+ sensitization and/or Ca2+-independent pathways. They also show that the TK pathway is involved in the tonic contraction associated with Ca2+ entry, whereas TK, PKC, and ROK mechanisms regulate Ca2+-independent signaling pathways or Ca2+sensitization.

Kinase cascades regulating entry into apoptosis

1997 ◽  
Vol 61 (1) ◽  
pp. 33-46
Author(s):  
P Anderson
Keyword(s):  
Cell Death ◽  
Cell Surface ◽  
Cell Survival ◽  
Tyrosine Kinases ◽  
Uv Light ◽  
Apoptotic Cell ◽  
Paracrine Factors ◽  
Surface Receptors ◽  
Promote Cell Survival ◽  
Necrosis Factor

All cells are constantly exposed to conflicting environment cues that signal cell survival or cell death. Survival signals are delivered by autocrine or paracrine factors that actively suppress a default death pathway. In addition to survival factor withdrawal, cell death can be triggered by environmental stresses such as heat, UV light, and hyperosmolarity or by dedicated death receptors (e.g., FAS/APO-1 and tumor necrosis factor [TNF] receptors) that are counterparts of growth factor or survival receptors at the cell surface. One of the ways that cells integrate conflicting exogenous stimuli is by phosphorylation (or dephosphorylation) of cellular constituents by interacting cascades of serine/threonine and tyrosine protein kinases (and phosphatases). Survival factors (e.g., growth factors and mitogens) activate receptor tyrosine kinases and selected mitogen-activated, cyclin-dependent, lipid-activated, nucleic acid-dependent, and cyclic AMP-dependent kinases to promote cell survival and proliferation, whereas environmental stress (or death factors such as FAS/APO-1 ligand and TNF-alpha) activates different members of these kinase families to inhibit cell growth and, under some circumstances, promote apoptotic cell death. Because individual kinase cascades can interact with one another, they are able to integrate conflicting exogenous stimuli and provide a link between cell surface receptors and the biochemical pathways leading to cell proliferation or cell death.

p21ras and protein kinase C function in distinct and interdependent signaling pathways in C3H 10T1/2 fibroblasts

1993 ◽  
Vol 13 (3) ◽  
pp. 1471-1479
Author(s):  
A Krook ◽  
M J Rapoport ◽  
S Anderson ◽  
H Pross ◽  
Y C Zhou ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Tyrosine Kinases ◽  
Signal Pathways ◽  
Mrna Levels ◽  
Ras Gene ◽  
Kinase C ◽  
Tetradecanoyl Phorbol Acetate ◽  
Cellular Signal

Both p21ras and protein kinase C (PKC) are believed to function downstream of plasma membrane-associated tyrosine kinases in cellular signal transduction pathways. However, it has remained controversial whether they function in the same pathway and, if so, what their relative position and functional relationship in such a pathway are. We investigated the possibilities that p21ras and PKC function either upstream or downstream of each other in a common linear pathway or that they function independently in colinear signal pathways. Either decreased expression of endogenous normal ras in fibroblasts transfected with an inducible antisense ras construct or overexpression of a mutant ras gene reduced the capacity of the phorbol ester tetradecanoyl phorbol acetate to trigger expression of the tetradecanoyl phorbol acetate-responsive and ras-dependent reporter gene osteopontin (OPN). PKC depletion decreased basal OPN mRNA levels, and the overexpression of ras restored OPN expression to the level of non-PKC-depleted cells. We propose a model in which ras and PKC function in distinct and interdependent signaling pathways.

scholarly journals Vav Family Proteins Couple to Diverse Cell Surface Receptors

2000 ◽  
Vol 20 (17) ◽  
pp. 6364-6373 ◽  
Author(s):  
Sheri L. Moores ◽  
Laura M. Selfors ◽  
Jessica Fredericks ◽  
Timo Breit ◽  
Keiko Fujikawa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Receptor Activation ◽  
Cell Surface Receptors ◽  
Nucleotide Exchange ◽  
Surface Receptors ◽  
Downstream Signaling

ABSTRACT Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. Vav proteins contain several protein binding domains which can link cell surface receptors to downstream signaling proteins. Vav1 is expressed exclusively in hematopoietic cells and tyrosine phosphorylated in response to activation of multiple cell surface receptors. However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple with similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. We expressed Vav1, Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav proteins to receptor activation. Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. Each Vav protein coprecipitated with activated epidermal growth factor and platelet-derived growth factor (PDGF) receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor were able to mediate Vav2 tyrosine phosphorylation. Integrin-induced tyrosine phosphorylation of Vav proteins was not detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT-dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NFκB-dependent transcription. Thus, although each Vav isoform can respond to similar cell surface receptors, there are isoform-specific differences in their activation of downstream signaling pathways.

Sign in / Sign up

Export Citation Format

Share Document