Signaling molecules tyrosine phosphorylation of paxillin and focal adhesion focal adhesions. Medical search. Frequent questions

PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. (wikipedia.org)
PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around). (wikipedia.org)
The PTK2 gene encodes a cytosolic protein tyrosine kinase that is found concentrated in the focal adhesions that form among cells attaching to extracellular matrix constituents. (wikipedia.org)
FAK tyrosine kinase activity can be activated, which plays a key important early step in cell migration. (wikipedia.org)
FAK is a highly conserved, non-receptor tyrosine kinase originally identified as a substrate for the oncogene protein tyrosine kinase v-src. (wikipedia.org)
Focal adhesion kinase has four defined regions, or tertiary structure domains. (wikipedia.org)
This interaction-thought to be the result of hydrophobic interactions between the two domains-prevents the activation of the Kinase domain, thereby preventing the signalling function of FAK. (wikipedia.org)
Here, we show that vinculin null (vin −/− ) cells and cells expressing a vinculin Y822F mutant have increased survival due to up-regulated activity of extracellular signal-regulated kinase (ERK). (rupress.org)
Both vinY822F and vin −/− cells exhibit increased interaction between paxillin and focal adhesion kinase (FAK) and increased paxillin and FAK phosphorylation. (rupress.org)
Podosomes are structurally divided into a core, which mainly contains proteins involved in actin polymerization (such as WASP, the Arp2/3 complex and cortactin ), and a surrounding ring populated by integrin receptors and adhesion proteins (for example, paxillin and focal adhesion kinase (FAK/Pyk2) ) [15] . (cellmigration.org)
We have identified a novel pathway that directs Lyn/Src family tyrosine kinase signals to the invadopodia to regulate sarcoma cell invasion via the molecule AFAP-1-like-1 (AFAP1L1), a new member of the AFAP (actin filament-associated protein) family. (nature.com)
AFAP1L1 intersects several invadopodia pathway components through its multiple domains and motifs, including the following (i) pleckstrin homology domains that bind phospholipids generated at the plasma membrane by phosphoinositide 3-kinase, (ii) a direct filamentous-actin binding domain and (iii) phospho-tyrosine motifs (pY136 and pY566) that specifically bind Vav2 and Nck2 SH2 domains, respectively. (nature.com)
Through its interaction with Vav2, AFAP1L1 regulates Rac activity and downstream control of PAK1/2/3 (p21-activated kinases) phosphorylation of myosin light chain (MLC) kinase and MLC2. (nature.com)
These data define a novel pathway that directs Lyn/Src family tyrosine kinase signals to sarcoma cell invadopodia through specific recruitment of Vav2 and Nck2 to phosphorylated AFAP1L1, to control cell migration and invasion. (nature.com)
Focal adhesion kinase (FAK) and steroid receptor coactivator (c-Src) are signaling proteins that regulate cytoskeletal dynamics and cell motility by influencing actin polymerization and focal adhesion turn-over [ 11 , 12 ]. (biomedcentral.com)
Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). (uci.edu)
FAK is a non-receptor tyrosine kinase involved in a wide variety of biological processes and crucial for embryonic development. (biologists.com)
FAK is composed of three major domains, the N-terminal FERM (4.1-band, ezrin, radixin, moesin) domain, followed by the central catalytic kinase domain and the C-terminal focal adhesion targeting (FAT) domain. (biologists.com)

A vinculin fragment (amino acids 811-1066) containing the paxillin binding site restored apoptosis and suppressed ERK activity in vin −/− cells. (rupress.org)
Thus, vinculin regulates survival and motility via ERK by controlling the accessibility of paxillin for FAK interaction. (rupress.org)
Although focal adhesions are similar, in terms of molecular composition, to nascent adhesions and focal complexes, several adhesion proteins appear to change as focal adhesions evolve in response to tension, e.g., zyxin and vinculin . (cellmigration.org)
Vinculin expression in focal adhesions upon EL treatment was determined by immunocytochemistry. (biomedcentral.com)

Nascent adhesions are the first observable adhesive structures, emerging within the lamellipodium. (cellmigration.org)
Nascent adhesions are small and highly transient - either maturing or disassembling ('turning over') - and are therefore not easily observed in every cell type [6] , [7] . (cellmigration.org)
They are larger than nascent adhesions, depend on myosin II for their formation and maintenance, and reside at the boundary of the lamellum and lamellipodium [10] , [11] . (cellmigration.org)
Like nascent adhesions, they also tend to either disassemble (turnover) or grow and elongate into focal adhesions. (cellmigration.org)
From left: Panel 1 shows formation of nascent adhesions at the cell periphery. (mechanobio.info)
Newly formed nascent adhesions gradually grow and change their protein composition to mature into FAs. (life-science-alliance.org)

This human sequence is highly conserved in rat and mouse paxillin. (ecmbio.com)
This signaling pathway is a highly conserved cell-to-cell communication system that regulates cell fate in development and disease. (5dok.org)

Eph/ephrin signaling is a cell-to-cell communication pathway, which regulates cell migration and proliferation. (5dok.org)
Here we showed that in migrating MDA-MB-231 cells Rab40c regulates focal adhesion's number, size, and distribution. (life-science-alliance.org)
Thus, we propose a model where Rab40c/CRL5 regulates ANKRD28 ubiquitylation and degradation, leading to a decrease in PP6 activity, which ultimately affects FAK and Hippo pathway signaling to alter focal adhesion dynamics. (life-science-alliance.org)
FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. (uci.edu)

Release of this auto-inhibitory interaction has been shown to occur within focal adhesions-but not in the cytoplasm-and therefore is thought to require interaction with focal adhesion proteins, potentially as a result of mechanical forces transmitted through the focal adhesion. (wikipedia.org)
Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small-protein ß2-microglobulin (ß2m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. (bvsalud.org)
Paxillin contains LD motifs, LIM domains, and an SH3- and SH2-binding domain that participate in a variety of protein-protein interactions with kinases, GTPase-activating proteins, and cytoskeletal proteins. (ecmbio.com)
Adhesion complexes (i.e., focal adhesions and focal complexes) and cell-cell contacts are specialized structures that harbor a large number of cytoskeletal proteins and one of the highest concentrations of signaling molecules in cells ( Ruoslahti and Obrink, 1996 ). (rupress.org)
Our data suggest that EL suppresses lung cancer cell motility and invasion by altering FAK activity and subsequent activation of downstream proteins needed for focal adhesion formation and cytoskeletal rearrangement. (biomedcentral.com)
Rho GTPase effectors are a large group of proteins and include actin nucleation promoting molecules, adaptors, as well as kinases. (biomedcentral.com)

These multiprotein complexes are capable of capturing and integrating many signals from the extracellular as well as intracellular environments ( Rosales and Juliano, 1995 ). (rupress.org)
other signaling adaptors are also recruited to these complexes, including FAK and paxillin. (cellmigration.org)
Focal complexes are adhesions in the early stages of maturation. (cellmigration.org)
We show that the FERM domain has a role in the recruitment of FAK on focal adhesions and controls the dynamics of the protein on these complexes. (biologists.com)
Rasipl null angioblasts fail to properly localize the polarity determinant Par3 and display defective cell polarity, resulting in mislocalized junctional complexes and loss of adhesion to extracellular matrix ( ECM ). (xenbase.org)

The encoded protein is a member of the FAK subfamily of protein tyrosine kinases that included PYK2, but lacks significant sequence similarity to kinases from other subfamilies. (wikipedia.org)
FAK is a protein of 125 kD recruited as a participant in focal adhesion dynamics between cells, and has a role in motility and cell survival. (wikipedia.org)
FAK is typically located at structures known as focal adhesions, which are multi-protein structures that link the extracellular matrix (ECM) to the cytoplasmic cytoskeleton. (wikipedia.org)
This antibody detects a 72kDa* protein corresponding to the molecular mass of phosphorylated paxillin on SDS-PAGE immunoblots of pervanadate treated A431 cells, but not in A431 control cells. (ecmbio.com)
Paxillin, an integrin-assembly protein, has four major tyrosine phosphorylation sites, and the phosphorylation of Tyr31 and Tyr118 correlates with cell adhesion and migration. (silverchair.com)
Gene and protein expression levels of FAK-Src signaling molecules in EL-treated lung cancer cells were determined using PCR arrays, qRT-PCR, and western blotting. (biomedcentral.com)

One of the main functions of FAs is to physically connect the cellular actin cytoskeleton to ECM, therefore sensing, integrating, and transducing extracellular signaling. (life-science-alliance.org)
Similarly, depletion of either Rasip1 or Arhgap29 in cultured ECs blocks in vitro lumen formation, fundamentally alters the cytoskeleton, and reduces integrin-dependent adhesion to ECM . (xenbase.org)

We hypothesized that EL could inhibit lung cancer cell motility by affecting the FAK-Src signaling pathway. (biomedcentral.com)

These adhesions are usually physically linked to large, readily visualized actomyosin bundles [13] , and their appearance correlates inversely with motility, such that they are conspicuously absent in cells migrating within a three-dimensional (3D) substrate. (cellmigration.org)
EL decreased phosphorylation of FAK and its downstream targets, Src, paxillin, and decreased mRNA expression of cell motility-related genes, RhoA, Rac1, and Cdc42 in lung cancer cells. (biomedcentral.com)
Therefore, there is a need for less toxic agents that target FAK-Src signaling and inhibit lung cancer cell motility. (biomedcentral.com)
The objective for this research was to identify EL as a less toxic agent to inhibit lung cancer cell motility, and to determine its anti-migratory mechanisms by focusing on FAK-Src signaling and down-stream effects. (biomedcentral.com)
Focal adhesions act as molecular clutches that provide grip to the substrate for the lamellipodium to protrude forward during motility. (mechanobio.info)

My laboratory is focused on understanding mechanisms of resistance to molecular targeting agents directed against receptor tyrosine kinases. (wisc.edu)
Monoclonal antibody therapy has been developed over the past 30 years to target receptor tyrosine kinases (RTKs), which sit on the outer membrane of cancerous cells. (wisc.edu)

Integrin receptors are heterodimeric transmembrane glycoproteins that cluster upon ECM engagement, leading to FAK phosphorylation and recruitment to focal adhesions. (wikipedia.org)
These sites may provide docking motifs for recruitment of other signaling molecules to focal adhesions. (ecmbio.com)
Whereas the formation of focal adhesions requires actomyosin-mediated contractile force mediated by RhoA , podosome formation is stimulated by a local loss of contractility and the recruitment of negative regulators of RhoA, such as p190RhoGAP [16] . (cellmigration.org)

We found that mutation of Tyr31/118 caused enhanced activation of RhoA and premature formation of stress fibers with substantial loss of efficient membrane spreading and ruffling in adhesion and migration of NMuMG cells. (silverchair.com)
EL treatment reduced the density and number of F-actin fibers in lung cancer cell lines, and reduced the number and size of focal adhesions. (biomedcentral.com)
In panel 2, some adhesions attach to stress fibers and grow in size while some disassemble (yellow with dotted outline) at the lamellipodium-lamellum boundary. (mechanobio.info)
The best-characterized molecules are Rho, which controls the stress fibers and focal adhesion formation, and Rac and Cdc42, which regulate membrane ruffling, and filopodium formation, respectively. (biomedcentral.com)

Scheme depicts the process of adhesion maturation. (cellmigration.org)
Fibrillar adhesions represent an extreme in the maturation of adhesions and are not generally seen in migrating cells. (cellmigration.org)
The protrusions of the cell edge are shown as green arrows corresponding to points of adhesion maturation (panels 3 and 4). (mechanobio.info)

These adhesions generate signals that activate Rac, promoting actin polymerization and preventing myosin II engagement in the lamellipodium. (cellmigration.org)
At the lamellipodium-lamellum interface, unstable adhesions disappear and stable ones start to elongate in a centripetal fashion along the direction of actin retrograde flow. (mechanobio.info)

Expression of FF blocks focal adhesion turnover and, unlike FRNK, acts as a dominant negative in vivo . (biologists.com)

Rho activation is thought to generate focal adhesions and actin bundling due to increased myosin II activity. (cellmigration.org)
These defects result from increased RhoA /ROCK/myosin II activity and blockade of Cdc42 and Rac1 signaling. (xenbase.org)

Tyrosine phosphorylation of paxillin occurs in response to growth factors, neuropeptides, and integrins. (ecmbio.com)

FAK activity elicits intracellular signal transduction pathways that promote the turn-over of cell contacts with the extracellular matrix, promoting cell migration. (wikipedia.org)
Cell adhesion (the physical interaction of a cell with another cell or with the extracellular matrix (ECM)) is essential for cell migration and tissue integrity. (cellmigration.org)

A carboxy-terminal region of one hundred and fifty-nine amino acids, the focal adhesion targeting domain (FAT), has been shown to be responsible for targeting FAK to focal adhesions. (wikipedia.org)
The function of the amino-terminal domain is less clear, but it has been shown to interact with the beta-1 integrin subunit in vitro and is thought to be involved in the transduction of signals from ECM-integrin clusters. (wikipedia.org)
Clone M102 was generated from phospho-Paxillin (Tyr-31) synthetic peptide (coupled to KLH) corresponding to amino acid residues around tyrosine 31 of human paxillin. (ecmbio.com)

Cell membranes are highly enriched in signaling receptors, transmembrane mechanosensors, pumps and channels, and, depending on their makeup, can recruit and retain a pool of mechanosensors important in the field of mechanobiology. (mechanobio.info)

Throughout apoptosis, FAK is an important contributor to cell rounding, loss of focal contacts and apoptotic membrane formations such as blebbing, which involves contracting the cortical actin ring and is followed by chromatin condensation and nuclear fragmentation. (wikipedia.org)
Transfection with paxillin Y31FY118F dominant-negative mutant in these cells inhibits ERK activation and restores apoptosis. (rupress.org)

Although their molecular composition is very similar to that of focal adhesions, their spatial distribution is radial, forming dot-like structures similar to 'suction cups' [14] . (cellmigration.org)

We found that Tyr31/118-phosphorylated paxillin competes with p190RhoGAP for binding to p120RasGAP, and provides evidence that p190RhoGAP freed from p120RasGAP efficiently suppresses RhoA activity during cell adhesion. (silverchair.com)
We conclude that Tyr31/118-phosphorylated paxillin serves as a template for the localized suppression of RhoA activity and is necessary for efficient membrane spreading and ruffling in adhesion and migration of NMuMG cells. (silverchair.com)

Paxillin is involved in focal adhesion formation during cell adhesion and migration. (ecmbio.com)
Cell-cell adhesion maintains epithelial tissues, supports functional contacts between specialized cells, and can facilitate directed migration (for example, radial glia can guide neuronal progenitor cells to specific layers of the brain). (cellmigration.org)
Cell-matrix adhesion is the best-studied form of adhesion that mediates cell migration, and is the focus of this outline. (cellmigration.org)
With nascent adhesion formation at the leading edge, the FAs at the cell rear need to be disassembled to promote rear end retraction and efficient cell migration. (life-science-alliance.org)

The N-terminal helix contains a phosphorylatable tyrosine (Y925) implicated in signal transduction. (wikipedia.org)

Phosphorylation of paxillin occurs at both tyrosine and serine sites. (ecmbio.com)

These signals are also required for the dissolution of some adhesions (turnover) as the cell advances. (cellmigration.org)

Both of these sites may be involved in Crk binding to paxillin during integrin-mediated cell adhesion. (ecmbio.com)
Owing to their highly localized nature, cell-matrix adhesions were initially called focal adhesions. (cellmigration.org)
Over the years, several types of cell-matrix adhesion have been described. (cellmigration.org)
While much is known about biochemical signaling, many of the mechanisms that drive cell outcome in response to biophysical influences remain to be uncovered. (5dok.org)
Panel 4 shows sliding of adhesion and hence slight retraction of the respective section of the cell edge compared to panel 3. (mechanobio.info)
We show that a fibronectin-derived signal transduced by FAK governs polarity and cell intercalation. (biologists.com)

Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation. (uci.edu)

The detection of mechanical signals, and their integration into biochemical pathways, is integral to the cell's ability to sense, measure and respond to its physical surroundings. (mechanobio.info)

Furthermore, we identified that phosphorylation of FAK and MOB1 is decreased in Rab40c knock-out cells, which may contribute to focal adhesion site regulation by Rab40c. (life-science-alliance.org)
In 2008 our lab was the first to report that tumor cells that acquired resistance to cetuximab exhibited dramatic up regulation of the EGFR, secondary to loss of ubiquitination, which led to enhanced signals to other EGFR family members (HER and HER3) that promoted proliferation and survival. (wisc.edu)
Blood vessel tubulogenesis requires Rasip1 regulation of GTPase signaling. (xenbase.org)

We have therefore investigated the role of matrix stiffness in Notch signaling in breast cancer cells. (5dok.org)
Aberrant Notch signaling in breast cancer has been found to correlate with invasion and patient outcome. (5dok.org)

What steps are involved in the formation of focal adhesions? (mechanobio.info)
The four panels represent roughly the different steps in the formation and disassembly of focal adhesions. (mechanobio.info)

During early apoptotic signaling in human endothelial cells, FAK is cleaved by caspase 3 at Asp-772, generating two FAK fragments of approximately 90 and 130 kDa in length. (wikipedia.org)
Podosomes are ring-shaped adhesions often found in fast-moving cells, such as macrophages. (cellmigration.org)
We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. (uci.edu)

Moreover, they transmit signals that contribute to the progression of lung cancer by promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunosuppression. (bvsalud.org)

Therefore, FAs are highly dynamic, and their number, size, and distribution can rapidly change in response to internal or external signals. (life-science-alliance.org)

The major sites of tyrosine phosphorylation include Tyr-31 and Tyr-118. (ecmbio.com)

Phosphorylated Tyr31/118 was found to bind to two src homology (SH)2 domains of p120RasGAP, with coprecipitation of endogenous paxillin with p120RasGAP. (silverchair.com)

Two hydrophobic patches between helices-one formed by the first and fourth helix, the other formed by the second and third helix-have been shown to bind short helical domains of Paxillin. (wikipedia.org)

Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control. (uci.edu)

Anatomy34

Organisms6

Diseases2

Chemicals and Drugs149

Analytical, Diagnostic and Therapeutic Techniques and Equipment16

Phenomena and Processes44

Disciplines and Occupations1

Information Science3

Kinase18

Vinculin4

Nascent adhesions6

Highly conserved2

Regulates4

Proteins6

Complexes5

Protein6

Cytoskeleton2

Pathway1

Motility5

Kinases2

Recruitment3

Fibers4

Maturation3

Lamellipodium2

FRNK1

Myosin II activity2

Integrins1

Extracellular matrix2

Amino3

Receptors1

Apoptosis2

Structures1

RhoA2

Migration4

Transduction1

Occurs1

Turnover1

Cell6

Expression1

Biochemical1

Regulation3

Breast Cancer2

Formation2

Cells3

Lung cancer1

Response1

Include1

Found1

Bind1

Control1