scholarly journals pHocal adhesion kinase regulation is on a FERM foundation

2013 ◽  
Vol 202 (6) ◽  
pp. 833-836
Author(s):  
Christine Lawson ◽  
David D. Schlaepfer
Keyword(s):  
Tumor Cells ◽  
Intracellular Ph ◽  
Focal Adhesion ◽  
Receptor Binding ◽  
Matrix Proteins ◽  
Integrin Receptor ◽  
Kinase Regulation ◽  
Cell Biol ◽  
Focal Adhesion Turnover

Increases in intracellular pH (pHi) occur upon integrin receptor binding to matrix proteins and in tumor cells. In this issue, Choi et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201308034) show that pHi increase activates FAK by causing deprotonation of histidine 58 in its FERM (band 4.1, ezrin, radixin, moesin) homology domain, which exposes a region important for FAK autophosphorylation. This model of FAK activation could contribute to motility of tumor cells by promoting focal adhesion turnover.

scholarly journals Modeling the Kinetics of Integrin Receptor Binding to Hepatic Extracellular Matrix Proteins

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Shanice V. Hudson ◽  
Christine E. Dolin ◽  
Lauren G. Poole ◽  
Veronica L. Massey ◽  
Daniel Wilkey ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Receptor Binding ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Integrin Receptor ◽  
Kinetics Of

scholarly journals Focal Adhesion Kinase Suppresses Apoptosis by Binding to the Death Domain of Receptor-Interacting Protein

2004 ◽  
Vol 24 (10) ◽  
pp. 4361-4371 ◽  
Author(s):  
Elena Kurenova ◽  
Li-Hui Xu ◽  
Xihui Yang ◽  
Albert S. Baldwin ◽  
Rolf J. Craven ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Tumor Cells ◽  
Focal Adhesion ◽  
Death Receptor ◽  
Human Tumors ◽  
Receptor Complex ◽  
Death Domain ◽  
Functional Link ◽  
Interacting Protein ◽  
Survival Signals

ABSTRACT Tumor cells resist the apoptotic stimuli associated with invasion and metastasis by activating survival signals that suppress apoptosis. Focal adhesion kinase (FAK), a tyrosine kinase that is overexpressed in a variety of human tumors, mediates one of these survival signals. Attenuation of FAK expression in tumor cells results in apoptosis that is mediated by caspase 8- and FADD-dependent pathways, suggesting that death receptor pathways are involved in the process. Here, we report a functional link between FAK and death receptors. We have demonstrated that FAK binds to the death domain kinase receptor-interacting protein (RIP). RIP is a major component of the death receptor complex and has been shown to interact with Fas and tumor necrosis factor receptor 1 through its binding to adapter proteins. We have shown that RIP provides proapoptotic signals that are suppressed by its binding to FAK. We thus propose that FAK overexpression in human tumors provides a survival signal function by binding to RIP and inhibiting its interaction with the death receptor complex.

scholarly journals Syndecan-4 Promotes Epithelial Tumor Cells Spreading and Regulates the Turnover of PKCα Activity under Mechanical Stimulation on the Elastomeric Substrates

2015 ◽  
Vol 36 (4) ◽  
pp. 1291-1304 ◽  
Author(s):  
Chun-Ping Huang ◽  
Chao-Min Cheng ◽  
Hong-Lin Su ◽  
Yi-Wen Lin
Keyword(s):  
Mechanical Stress ◽  
Tumor Cells ◽  
Focal Adhesion ◽  
Mechanical Stimulation ◽  
Binding Motif ◽  
Epithelial Tumor ◽  
Cell Contractility ◽  
Myosin Light Chain 2 ◽  
Epithelial Tumor Cells ◽  
Time Courses

Background: Heparan sulfate proteoglycans (HSPGs) at the cell surface play an important role in cell adhesion, spreading, formation of focal adhesion complexes (FACs), and sensing mechanical stress. Syndecans are members of the HSPGs family and are highly expressed in various tumor cells. Syndecan-4 (SDC4) is a unique member of syndecans that activates protein kinase C alpha (PKCα). However, syndecan-4 in tumor cells development is not clear when receiving mechanical stress. Aims: Here we investigate the role of syndecan-4 in tumor cells spreading and its downstream kinases under mechanical stimulation. Methods: Epithelial tumor cells were seeded onto elastomeric polydimethylsiloxane (PDMS) membranes coated with poly-L-lysine (Pl), fibronectin (Fn), or anti-SDC4 antibody and stretched with a modified pressure-driven cell-stretching (PreCS) device. Results: When cells received mechanical stimulation, engagement of syndecan-4 promoted the phosphorylation of focal adhesion kinase (FAK) at tyrosine 397 and PKCα at serine 657. Furthermore, we analyzed the cell contractility marker—myosin light chain 2 (MLC2) in 30 min time courses. The levels of phosphorylated MLC2 at serine19 were augmented through ligations of syndecan-4 but not integrin binding motif (RGD) at 10 min mechanical stimulation and were suppressed at 30 min and this phenomenon was associated with the activity of PKCα. Conclusion: Our data demonstrate that syndecan-4 is essential for transmitting the mechanotransduction signals via activation of PKCα and is important for tumor cells spreading, assembly of actin cytoskeleton and cell contractility.

scholarly journals Focal Adhesion Kinase Regulation of Mechanotransduction and its Impact on Endothelial Cell Functions

2012 ◽  
Vol 83 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Noureddine Zebda ◽  
Oleksii Dubrovskyi ◽  
Konstantin G. Birukov
Keyword(s):  
Endothelial Cell ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Kinase Regulation ◽  
Cell Functions

A novel, tissue-specific integrin subunit, beta nu, expressed in the midgut of Drosophila melanogaster

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 845-858 ◽  
Author(s):  
G.H. Yee ◽  
R.O. Hynes
Keyword(s):  
Drosophila Melanogaster ◽  
Matrix Proteins ◽  
Beta Subunits ◽  
Integrin Subunit ◽  
Integrin Receptor ◽  
Tissue Specific ◽  
Surface Receptors ◽  
Polymerase Chain ◽  
Maximal Expression

The integrins are a family of cell surface receptors for extracellular matrix proteins and counter-receptors on other cells. We have used the polymerase chain reaction to identify a novel integrin receptor beta subunit in Drosophila melanogaster. The deduced amino acid sequence of this subunit, which we have termed beta v (beta-neu), indicates that it has several unusual properties. The beta v subunit is roughly 33% identical with each of the previously sequenced vertebrate and Drosophila beta subunits and is lacking four of the 56 cysteine residues characteristic of most members of this protein family. The expression of the beta v gene is strikingly restricted. It is temporally regulated, with maximal expression occurring at 12–15 hours of embryonic development. In situ hybridization analyses and antibody localization on whole-mount embryos reveal that beta v expression is tissue-specific and confined to the developing midgut endoderm and its precursors during embryogenesis. Tissue specificity of expression is maintained through later stages of development as beta v transcripts are found exclusively in the larval midgut. Within this structure, beta v transcripts are especially concentrated in the cells of the midgut imaginal islands which give rise to the adult midgut.

Cyclic GMP-dependent protein kinase is required for thrombospondin and tenascin mediated focal adhesion disassembly

1996 ◽  
Vol 109 (10) ◽  
pp. 2499-2508 ◽  
Author(s):  
J.E. Murphy-Ullrich ◽  
M.A. Pallero ◽  
N. Boerth ◽  
J.A. Greenwood ◽  
T.M. Lincoln ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Focal Adhesion ◽  
Kinase Activity ◽  
Catalytic Domain ◽  
Focal Adhesions ◽  
Matrix Proteins ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

Focal adhesions are specialized regions of cell membranes that are foci for the transmission of signals between the outside and the inside of the cell. Intracellular signaling events are important in the organization and stability of these structures. In previous work, we showed that the counter-adhesive extracellular matrix proteins, thrombospondin, tenascin, and SPARC, induce the disassembly of focal adhesion plaques and we identified the active regions of these proteins. In order to determine the mechanisms whereby the anti-adhesive matrix proteins modulate cytoskeletal organization and focal adhesion integrity, we examined the role of protein kinases in mediating the loss of focal adhesions by these proteins. Data from these studies show that cGMP-dependent protein kinase is necessary to mediate focal adhesion disassembly triggered by either thrombospondin or tenascin, but not by SPARC. In experiments using various protein kinase inhibitors, we observed that selective inhibitors of cyclic GMP-dependent protein kinase, KT5823 and Rp-8-Br-cGMPS, blocked the effects of both the active sequence of thrombospondin 1 (hep I) and the alternatively-spliced segment (TNfnA-D) of tenascin-C on focal adhesion disassembly. Moreover, early passage rat aortic smooth muscle cells which have high levels of cGMP-dependent protein kinase were sensitive to hep I treatment, in contrast to passaged cGMP-dependent protein kinase deficient cells which were refractory to hep I or TNfnA-D treatment, but were sensitive to SPARC. Transfection of passaged smooth muscle cells with the catalytic domain of PKG I alpha restored responsiveness to hep I and TNfnA-D. While these studies show that cGMP-dependent protein kinase activity is necessary for thrombospondin and tenascin-mediated focal adhesion disassembly, kinase activity alone is not sufficient to induce disassembly as transfection of the catalytic domain of the kinase in the absence of additional stimuli does not result in loss of focal adhesions.

scholarly journals Beware of thy neighbor: Senescent cancer cells feast on adjacent cells to persist

2019 ◽  
Vol 218 (11) ◽  
pp. 3535-3536
Author(s):  
Marco Napoli ◽  
Elsa R. Flores
Keyword(s):  
Patient Outcome ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Poor Patient ◽  
Poor Patient Outcome ◽  
Cell Biol

Chemotherapy-resistant tumor cells are responsible for poor patient outcome. In this issue, Tonnessen-Murray et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201904051) elegantly show that chemotherapy triggers macrophage-like features in surviving cancer cells, which in turn phagocyte normal and tumor cells alike to outlast dormancy and cause relapse.

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