Complexes of tetraspanins with integrins: more than meets the eye

2001 ◽  
Vol 114 (23) ◽  
pp. 4143-4151 ◽  
Author(s):  
Fedor Berditchevski
Keyword(s):  
Cell Migration ◽  
Distinct Type ◽  
Cell Periphery ◽  
Diverse Range ◽  
Kinase C ◽  
Biological Phenomena ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Dependent Cell ◽  
Phosphatidylinositol 4

The transmembrane proteins of the tetraspanin superfamily are implicated in a diverse range of biological phenomena, including cell motility, metastasis, cell proliferation and differentiation. The tetraspanins are associated with adhesion receptors of the integrin family and regulate integrin-dependent cell migration. In cells attached to the extracellular matrix, the integrin-tetraspanin adhesion complexes are clustered into a distinct type of adhesion structure at the cell periphery. Various tetraspanins are associated with phosphatidylinositol 4-kinase and protein kinase C isoforms, and they may facilitate assembly of signalling complexes by tethering these enzymes to integrin heterodimers. At the plasma membrane, integrin-tetraspanin signalling complexes are partitioned into specific microdomains proximal to cholesterol-rich lipid rafts. A substantial fraction of tetraspanins colocalise with integrins in various intracellular vesicular compartments. It is proposed that tetraspanins can influence cell migration by one of the following mechanisms: (1) modulation of integrin signalling; (2) compartmentalisation of integrins on the cell surface; or (3) direction of intracellular trafficking and recycling of integrins.

scholarly journals Cell cycle-dependent phosphorylation and regulation of cellular differentiation

2018 ◽  
Vol 46 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
Laura J.A. Hardwick ◽  
Roberta Azzarelli ◽  
Anna Philpott
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Diverse Range ◽  
Cyclin Dependent Kinases ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Cycle Dependent ◽  
Cell Cycle Dynamics ◽  
Bidirectional Interactions

Embryogenesis requires an exquisite regulation of cell proliferation, cell cycle withdrawal and differentiation into a massively diverse range of cells at the correct time and place. Stem cells also remain to varying extents in different adult tissues, acting in tissue homeostasis and repair. Therefore, regulated proliferation and subsequent differentiation of stem and progenitor cells remains pivotal throughout life. Recent advances have characterised the cell cycle dynamics, epigenetics, transcriptome and proteome accompanying the transition from proliferation to differentiation, revealing multiple bidirectional interactions between the cell cycle machinery and factors driving differentiation. Here, we focus on a direct mechanistic link involving phosphorylation of differentiation-associated transcription factors by cell cycle-associated Cyclin-dependent kinases. We discuss examples from the three embryonic germ layers to illustrate this regulatory mechanism that co-ordinates the balance between cell proliferation and differentiation.

Protein kinase C: a target for anticancer drugs?

2003 ◽  
pp. 389-396 ◽  
Author(s):  
H J Mackay ◽  
C J Twelves
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Anticancer Therapy ◽  
Kinase C ◽  
Cell Proliferation And Differentiation ◽  
Selective Targeting ◽  
Proliferation And Differentiation ◽  
Tumour Cell Invasion ◽  
Suitable Target

Protein kinase C (PKC) is a family of serine/threonine kinases that is involved in the transduction of signals for cell proliferation and differentiation. The important role of PKC in processes relevant to neoplastic transformation, carcinogenesis and tumour cell invasion renders it a potentially suitable target for anticancer therapy. Furthermore, there is accumulating evidence that selective targeting of PKC may improve the therapeutic efficacy of established neoplastic agents and sensitise cells to ionising radiation. This article reviews the rationale for targeting PKC, focuses on its role in breast cancer and reviews the preclinical and clinical data available for the efficacy of PKC inhibition.

Diacylglycerol-induced shape changes, movements and altered F-actin distribution in human neutrophils

1988 ◽  
Vol 90 (4) ◽  
pp. 657-666 ◽  
Author(s):  
A. Zimmermann ◽  
P. Gehr ◽  
H.U. Keller
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Spherical Shape ◽  
Distinct Type ◽  
Human Neutrophils ◽  
Neutrophil Granulocytes ◽  
Cell Periphery ◽  
Locomotor Apparatus ◽  
Kinase C ◽  
Shape Changes

The study shows that diacylglycerols (DAGs) as physiological activators of protein kinase C induce characteristic shape changes in human neutrophil granulocytes. In contrast to chemotactic peptides, which can induce front-tail polarity characterized by a contracted tail and an expanding front, DAGs elicit the formation of non-polar cells with surface projections. These cells exhibit a distinct type of motility characterized by vigorous and continuous shape changes without front-tail polarity and without the unidirectional movement and cytoplasmic streaming seen in polarized cells. In neutrophils exposed to DAGs, F-actin is shifted to the cell periphery and mainly into the surface projections of activated cells. DAGs induce the formation of large intracellular vacuoles in neutrophils producing surface projections, and these vacuoles persist after the cells have reacquired a spherical shape. Combined stimulation of human neutrophils with DAG and fNLPNTL results in a suppression of peptide-induced polarity and the formation of non-polar motile cells resembling those stimulated with DAG alone. These results suggest that the diacylglycerol-protein kinase C pathway may be instrumental in transducing or modulating signals to both the locomotor apparatus and the exocytotic and/or pinocytic system of the cell. Neutrophil stimulation with DAGs thus represents a useful model with which to study further the hypothesis that distinct types of neutrophil shapes and movements are preferentially associated with distinct functions and to characterize signalling pathways.

scholarly journals Homodimerization of Erythropoietin Receptor by a Bivalent Monoclonal Antibody Triggers Cell Proliferation and Differentiation of Erythroid Precursors

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 473-482 ◽  
Author(s):  
Helmut Schneider ◽  
Warak Chaovapong ◽  
David J. Matthews ◽  
Cyrus Karkaria ◽  
Robert T. Cass ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mathematic Model ◽  
Receptor Activation ◽  
Erythropoietin Receptor ◽  
Fab Fragment ◽  
Erythroid Progenitor ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Erythroid Precursors ◽  
Dependent Cell

Abstract Erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Several lines of evidence indicate that the most likely mechanism of EPO receptor (EPO-R) activation by EPO is homodimerization of the receptor on the surface of erythrocyte precursors. Therefore, we argued that it should be possible to raise EPO-R monoclonal antibodies (MoAbs) that would activate the receptor by dimerization and thus mimic EPO action. We have identified such an agonist MoAb (MoAb34) directed against the extracellular EPO binding domain of the EPO-R. This bivalent IgG antibody triggers the proliferation of EPO-dependent cell lines and induces differentiation of erythroid precursors in vitro. In contrast, the monovalent Fab fragment, which cannot dimerize the receptor, is completely inactive. The mechanism of receptor activation by homodimerization implies that at high ligand concentrations the formation of 1:1 receptor/ligand complexes is favored over 2:1 complexes, thereby turning the ligand agonist into an antagonist. Thus, EPO and MoAb34 should self-antagonize at high concentrations in both cell proliferation and differentiation assays. Our data indeed demonstrate that EPO and MoAb34 antagonize ligand-dependent cell proliferation with IC50 values of approximately 20 and 2 μmol/L, respectively. Erythroid colony formation (BFUe) is inhibited at MoAb34 concentrations above 1 μmol/L. Furthermore, we analyzed the MoAb34:EPO-R interaction using a mathematic model describing antibody-mediated receptor dimerization. The data for proliferation and differentiation activity were consistent with the receptor dimer formation on the cell surface predicted by the model.

Protein kinase C involvement in cell cycle modulation

2014 ◽  
Vol 42 (5) ◽  
pp. 1471-1476 ◽  
Author(s):  
Alessandro Poli ◽  
Sara Mongiorgi ◽  
Lucio Cocco ◽  
Matilde Y. Follo
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Cell Models ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Kinase C ◽  
Cell Proliferation And Differentiation ◽  
Cell Cycle Modulation ◽  
Proliferation And Differentiation

Protein kinases C (PKCs) are a family of serine/threonine kinases which act as key regulators in cell cycle progression and differentiation. Studies of the involvement of PKCs in cell proliferation showed that their role is dependent on cell models, cell cycle phases, timing of activation and localization. Indeed, PKCs can positively and negatively act on it, regulating entry, progression and exit from the cell cycle. In particular, the targets of PKCs resulted to be some of the key proteins involved in the cell cycle including cyclins, cyclin-dependent kinases (Cdks), Cip/Kip inhibitors and lamins. Several findings described roles for PKCs in the regulation of G1/S and G2/M checkpoints. As a matter of fact, data from independent laboratories demonstrated PKC-related modulations of cyclins D, leading to effects on the G1/S transition and differentiation of different cell lines. Moreover, interesting data were published on PKC-mediated phosphorylation of lamins. In addition, PKC isoenzymes can accumulate in the nuclei, attracted by different stimuli including diacylglycerol (DAG) fluctuations during cell cycle progression, and target lamins, leading to their disassembly at mitosis. In the present paper, we briefly review how PKCs could regulate cell proliferation and differentiation affecting different molecules related to cell cycle progression.

Protein Kinase C in Cell Proliferation and Differentiation

1988 ◽  
Vol 551 (1 Membrane in C) ◽  
pp. 369-371 ◽  
Author(s):  
SERGIO ADAMO ◽  
CLARA NERVI ◽  
ROBERTA CECI ◽  
LUCIANA DE ANGELIS ◽  
MARIO MOLINARO
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase C ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation
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