scholarly journals Protein tyrosine kinase 6 protects cells from anoikis by directly phosphorylating focal adhesion kinase and activating AKT

Oncogene ◽  
2012 ◽  
Vol 32 (36) ◽  
pp. 4304-4312 ◽  
Author(s):  
Y Zheng ◽  
J Gierut ◽  
Z Wang ◽  
J Miao ◽  
J M Asara ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Protein Tyrosine Kinase ◽  
Protein Tyrosine

scholarly journals Cloning and Characterization of Cell Adhesion Kinase β, a Novel Protein-tyrosine Kinase of the Focal Adhesion Kinase Subfamily

1995 ◽  
Vol 270 (36) ◽  
pp. 21206-21219 ◽  
Author(s):  
Hiroko Sasaki ◽  
Kazuko Nagura ◽  
Masaho Ishino ◽  
Hirotoshi Tobioka ◽  
Kiyoshi Kotani ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Tyrosine Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Protein Tyrosine Kinase ◽  
Protein Tyrosine ◽  
Kinase Subfamily ◽  
Novel Protein

scholarly journals Endothelin-1 stimulates tyrosine phosphorylation of p125 focal adhesion kinase in mesangial cells.

1995 ◽  
Vol 6 (5) ◽  
pp. 1504-1510
Author(s):  
M Haneda ◽  
R Kikkawa ◽  
D Koya ◽  
T Shikano ◽  
T Sugimoto ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tyrosine Kinase ◽  
Focal Adhesion Kinase ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Protein Tyrosine Kinase ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Protein Tyrosine ◽  
Endothelin 1

Endothelin-1 (ET-1) is known to induce the contraction and proliferation of glomerular mesangial cells. Because ET-1 was found to stimulate the tyrosine phosphorylation of unidentified cellular proteins in cultured mesangial cells, protein tyrosine kinase might serve as one of the important signals leading to various functions of ET-1. Focal adhesion kinase (p125FAK) is a newly identified cytoplasmic protein tyrosine kinase that is activated by the phosphorylation of its own tyrosine residue. Because p125FAK was found to play a role in the signal transduction of not only integrins but also various neurotransmitters, including bombesin, endothelin, and vasopressin in Swiss 3T3 cells and Rat-1 fibroblasts, whether ET-1 could stimulate the tyrosine phosphorylation of p125FAK in glomerular mesangial cells was examined. ET-1 stimulated the tyrosine phosphorylation of p125FAK by threefold to fourfold in cultured mesangial cells. This effect of ET-1 was detected at 1 min and reached a maximum within 5 min and was blocked by BQ-123, an antagonist for ETA receptor. A23187, a calcium ionophore, failed to stimulate the tyrosine phosphorylation of p125FAK, and ET-1 was able to stimulate the tyrosine phosphorylation of p125FAK, even in a calcium-free medium. The activation of protein kinase C (PKC) by phorbol 12, 13-dibutyrate resulted in a stimulation of the tyrosine phosphorylation of p125FAK, and an inhibition of PKC by calphostin C or staurosporine significantly reduced the effect of ET-1. Furthermore, prolonged treatment of the cells with phorbol 12, 13-dibutyrate markedly inhibited the ET-1-induced tyrosine phosphorylation of p125FAK. These results indicate that p125FAK might play a role in a signal transduction system of ET-1 in glomerular mesangial cells and that the ET-1-induced tyrosine phosphorylation of p125FAK is largely dependent on the PKC pathway.

scholarly journals Stretch of β1 Integrin Activates an Outwardly Rectifying Chloride Current via FAK and Src in Rabbit Ventricular Myocytes

2003 ◽  
Vol 122 (6) ◽  
pp. 689-702 ◽  
Author(s):  
David M. Browe ◽  
Clive M. Baumgarten
Keyword(s):  
Tyrosine Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Protein Tyrosine Kinase ◽  
Ventricular Myocytes ◽  
Mechanical Stretch ◽  
Left Ventricular ◽  
Cell Swelling ◽  
Β1 Integrin ◽  
Protein Tyrosine

Osmotic swelling of cardiac myocytes and other types of cells activates an outwardly rectifying, tamoxifen-sensitive Cl− current, ICl,swell, but it is unclear whether Cl− currents also are activated by direct mechanical stretch. We tested whether specific stretch of β1-integrin activates a Cl− current in rabbit left ventricular myocytes. Paramagnetic beads (4.5-μm diameter) coated with mAb to β1-integrin were applied to the surface of myocytes and pulled upward with an electromagnet while recording whole-cell current. In solutions designed to isolate anion currents, β1-integrin stretch elicited an outwardly rectifying Cl− current with biophysical and pharmacological properties similar to those of ICl,swell. Stretch-activated Cl− current activated slowly (t1/2 = 3.5 ± 0.1 min), partially inactivated at positive voltages, reversed near ECl, and was blocked by 10 μM tamoxifen. When stretch was terminated, 64 ± 8% of the stretch-induced current reversed within 10 min. Mechanotransduction involved protein tyrosine kinase. Genistein (100 μM), a protein tyrosine kinase inhibitor previously shown to suppress ICl,swell in myocytes, inhibited stretch-activated Cl− current by 62 ± 6% during continued stretch. Because focal adhesion kinase and Src are known to be activated by cell swelling, mechanical stretch, and clustering of integrins, we tested whether these tyrosine kinases mediated the response to β1-integrin stretch. PP2 (10 μM), a selective blocker of focal adhesion kinase and Src, fully inhibited the stretch-activated Cl− current as well as part of the background Cl− current, whereas its inactive analogue PP3 (10 μM) had no significant effect. In addition to activating Cl− current, stretch of β1-integrin also appeared to activate a nonselective cation current and to suppress IK1. Integrins are the primary mechanical link between the extracellular matrix and cytoskeleton. The present results suggest that integrin stretch may contribute to mechano-electric feedback in heart, modulate electrical activity, and influence the propensity for arrhythmogenesis.

scholarly journals Protein tyrosine kinase 2 beta (PTK2B), but not focal adhesion kinase (FAK), is expressed in a sexually dimorphic pattern in developing mouse gonads

2010 ◽  
Vol 239 (10) ◽  
pp. 2735-2741 ◽  
Author(s):  
Annemiek Beverdam ◽  
Terje Svingen ◽  
Stefan Bagheri-Fam ◽  
Peter McClive ◽  
Andrew H. Sinclair ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Protein Tyrosine Kinase ◽  
Sexually Dimorphic ◽  
Protein Tyrosine ◽  
Tyrosine Kinase 2 ◽  
Protein Tyrosine Kinase 2

scholarly journals Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains.

1995 ◽  
Vol 130 (5) ◽  
pp. 1181-1187 ◽  
Author(s):  
M D Schaller ◽  
C A Otey ◽  
J D Hildebrand ◽  
J T Parsons
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Cytoplasmic Domain ◽  
Embryo Cell ◽  
Vitro Assay ◽  
Protein Tyrosine ◽  
Signaling Complex

The integrins have recently been implicated in signal transduction. A likely mediator of integrin signaling is focal adhesion kinase (pp125FAK or FAK), a structurally distinct protein tyrosine kinase that becomes enzymatically activated upon engagement of integrins with their ligands. A second candidate signaling molecule is paxillin, a focal adhesion associated, cytoskeletal protein that coordinately becomes phosphorylated on tyrosine upon activation of pp125FAK. Paxillin physically complexes with two protein tyrosine kinases, pp60src and Csk (COOH-terminal src kinase), and the oncoprotein p47gag-crk, each of which could function as part of a paxillin signaling complex. Using an in vitro assay we have established that the cytoplasmic domain of the beta 1 integrin can bind to paxillin and pp125FAK from chicken embryo cell lysates. The NH2-terminal, noncatalytic domain of pp125FAK can bind directly to the cytoplasmic tail of beta 1 and recognizes integrin sequences distinct from those involved in binding to alpha-actinin. Paxillin binding is independent of pp125FAK binding despite the fact that both bind to the same region of beta 1. These results demonstrate that the cytoplasmic domain of the beta subunits of integrins contain binding sites for both signaling molecules and structural proteins suggesting that integrins can coordinate the generation of cytoplasmic signals in addition to their role in anchoring components of the cytoskeleton.

Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK

1993 ◽  
Vol 13 (2) ◽  
pp. 785-791
Author(s):  
M D Schaller ◽  
C A Borgman ◽  
J T Parsons
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Protein Tyrosine Kinase ◽  
Signal Transduction Pathway ◽  
Focal Adhesions ◽  
Cellular Adhesion ◽  
Protein Tyrosine ◽  
Intracellular Signals ◽  
Embryo Cells

Integrins play a central role in cellular adhesion and anchorage of the cytoskeleton and participate in the generation of intracellular signals, including tyrosine phosphorylation. We have recently isolated a cDNA encoding a unique, focal adhesion-associated protein tyrosine kinase (FAK) that is a component of an integrin-mediated signal transduction pathway. Here we report the isolation of cDNAs encoding the C-terminal, noncatalytic domain of the FAK kinase, termed FRNK (FAK-related nonkinase). Both the FAK- and FRNK-encoded polypeptides, pp125FAK and p41/p43FRNK, are expressed in normal chicken embryo cells. pp125FAK and p41/p43FRNK were localized to focal adhesions, suggesting that pp125FAK is directed to the focal adhesions by sequences within its C-terminal domain. We also show that the fibronectin-dependent increase in tyrosine phosphorylation of pp125FAK is accompanied by a concomitant posttranslational modification of p41FRNK.

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