• 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 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)
  • In addition, TRIP6 associates with the components of focal complexes including paxillin, focal adhesion kinase, c-Src, and p130 cas in an agonist-dependent manner. (ntnu.edu.tw)
  • In vitro experiments further confirmed that the extract significantly inhibited the phosphorylation of focal adhesion kinase (FAK), PI3K and Akt, and the expression of glucose metabolism-related proteins. (bvsalud.org)
  • In this study, we identified focal adhesion kinase (FAK) as a critical contributor to lenvatinib resistance in HCC. (bvsalud.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)
  • The ArfGAP paxillin kinase linker (PKL)/G protein-coupled receptor kinase-interacting protein (GIT)2 continues to be implicated in regulating cell spreading and motility through its transient recruitment of the p21-activated kinase (PAK) to focal adhesions. (healthyguide.info)
  • p21-activated kinase 4 (PAK4), a specific effector of the Rho GTPase Cdc42, is activated by HGF, and we have previously shown that activated PAK4 induces a loss of both actin stress fibres and focal adhesions. (silverchair.com)
  • 1990). Kinetic studies have suggested that localization of tensin and focal adhesion kinase to sites of integrin clustering are also early events in the formation of focal adhesions (Miyamoto et al. (ppbhg.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)
  • Many proteins in adhesion plaque such as integrin, cytoskeleton proteins, proteases, protein kinases, phosphatases take part in signal transferring by co-localizing with vinculin and talin [ 3 ]. (omicsonline.org)
  • A lager expansion of the cell area accompanied by a greater development of actin cytoskeleton and talin1, a greater adhesion strength of CTEs to each disk, and higher gene expression level of focal adhesion protein were observed with the mirror-polished surface than the mechanically polished surface both Ti and Ce-TZP/Al 2 O 3 disks. (alliedacademies.org)
  • Mirror-polished Ce-TZP/Al 2 O 3 might contribute to the success of implant therapy by its strong adhesion strength to gingival connective tissues with the developed focal contact-cytoskeleton complex. (alliedacademies.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)
  • ILK forms an obligate heterotrimeric complex with particularly interesting Cys-His-rich protein (PINCH) and parvin, which together lend stability to the actin cytoskeleton at focal adhesions ( Brakebusch and Fässler, 2003 ). (jneurosci.org)
  • RESULTS Identification of a 95-kDa Tyrosine Phosphorylated Nck-binding Protein The SH3-SH3-SH3-SH2 adaptor protein Nck is a major downstream mediator of extracellular matrix and growth element receptor signaling to the cytoskeleton through its ability to associate with receptor tyrosine kinases PAK and the WASP/WAVE complex (Buday and indicated like a Box-and-Whiskers Storyline (Number 10B). (healthyguide.info)
  • Migration and invasion require coordinated reorganisation of the actin cytoskeleton and regulation of cell-adhesion dynamics. (silverchair.com)
  • From left: Panel 1 shows formation of nascent adhesions at the cell periphery. (mechanobio.info)
  • 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)
  • 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)
  • Newly formed nascent adhesions gradually grow and change their protein composition to mature into FAs. (life-science-alliance.org)
  • 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)
  • There are specific receptor proteins like integrin on the external surface of focal attachments. (omicsonline.org)
  • We prepared Titanium (Ti) and Ce-TZP/Al 2 O 3 disks with different surface roughness, namely, mirrored and machined surfaces, on which HGF-1 were cultured, and then the biological parameters of the cultured cells, including cell morphology and gene expression of focal adhesion proteins were assessed. (alliedacademies.org)
  • Comparative functional multiomics showed that blood proteins induce distinct receptor-mediated transcriptional programs in microglia and macrophages, such as redox, type I interferon and lymphocyte recruitment. (nature.com)
  • We report a blood-induced microglia gene network and show that blood proteins elicit distinct receptor-mediated transcriptional changes and signaling programs in innate immune cells. (nature.com)
  • All other tissues appeared normal, suggesting that, in most cases, tensin's diverse functions are redundant and may be compensated for by other focal adhesion proteins. (ppbhg.org)
  • At the core of the focal adhesion is a cluster of activated integrin heterodimers, which are transmembrane signaling proteins that attach cells to their ligands, i.e., extracellular matrix (ECM)1 (Hynes, 1992). (ppbhg.org)
  • 1995). Of the myriad of focal adhesion proteins, tensin is particularly interesting because it has the ability to bind to actin microfilaments at multiple sites, enabling tensin both to cap the growing (barbed) ends of actin filaments and to cross-link actin filaments (Lo et al. (ppbhg.org)
  • our data imply that, in the kidney, loss of tensin leads to alpha-Boswellic acid a weakening, rather than a severing, of focal adhesion. (ppbhg.org)
  • Here we show that LPA stimulation promotes the interaction of the LPA 2 receptor with a focal adhesion molecule, TRIP6 (thyroid receptor interacting protein 6)/ZRP-1 (zyxin-related protein 1). (ntnu.edu.tw)
  • 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)
  • 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)
  • Therefore abrogation of appropriate temporal-spatial rules of PKL profoundly impairs normal cell adhesion dynamics consistent with a critical part for this protein Panobinostat and its binding partners. (healthyguide.info)
  • 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)
  • LPA-dependent recruitment of TRIP6 to the plasma membrane promotes its targeting to focal adhesions and co-localization with actin stress fibers. (ntnu.edu.tw)
  • 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)
  • The protrusions of the cell edge are shown as green arrows corresponding to points of adhesion maturation (panels 3 and 4). (mechanobio.info)
  • 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)
  • providing a ligand for the α6β1 integrin receptor expressed by OLs. (jneurosci.org)
  • Lysophosphatidic acid (LPA) induces actin rearrangement, focal adhesion assembly, and cell migration through the activation of small G protein Rho and its downstream effectors. (ntnu.edu.tw)
  • Cetuximab (IMC- C225, Erbitux) prevents receptor activation and dimerization and ultimately induces receptor internalization and. (wisc.edu)
  • 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)
  • Focal adhesions act as molecular clutches that provide grip to the substrate for the lamellipodium to protrude forward during motility. (mechanobio.info)
  • 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)
  • 1995). Focal adhesions were first identified in tissue-culture cells, as sites of contact between a cell and its underlying substrate (Abercrombie et al. (ppbhg.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)
  • These adhesions generate signals that activate Rac, promoting actin polymerization and preventing myosin II engagement in the lamellipodium. (cellmigration.org)
  • 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)
  • Focal attachments have 10-15 nm distance between the cell membrane and the material surface and they are tight connections. (omicsonline.org)
  • These signals are also required for the dissolution of some adhesions (turnover) as the cell advances. (cellmigration.org)
  • Moreover, these cells have a concomitant reduction in cell-adhesion turnover rates. (silverchair.com)
  • Taken together, our results suggest that TRIP6 functions at a point of convergence between the activated LPA 2 receptor and downstream signals involved in cell adhesion and migration. (ntnu.edu.tw)
  • Throughout cell-material interaction, adhesion is influenced by the features of a biomaterial surface, comprising topography and physicochemical properties. (alliedacademies.org)
  • The adhesions between cultured cells and the material surface are called focal attachments or adhesion plaques. (omicsonline.org)
  • Notably both GFP-PKL Triple YF and GFP-PaxillinΔLD4-expressing cells displayed higher fluctuations in protrusion area changes prominently indicated from the span (minimum amount and maximum value) of the "whiskers. (healthyguide.info)
  • Overexpression of the nonphosphorylated GFP-PKL Triple YF mutant stimulates cell distributing and protrusiveness much like overexpression of a paxillin mutant that does not bind PKL suggesting that failure to recruit PKL to focal adhesions interferes with normal cell distributing and motility. (healthyguide.info)
  • Gene amplification, overexpression and hyperactivity of the epidermal growth factor receptor (EGFR) is frequently observed in non-small cell lung cancer (NSCLC), head and neck cancer (HNSCC), breast and colorectal cancer (CRC). (wisc.edu)
  • 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)
  • DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is the prototypic endocytic receptor of dendritic cells, whose ligands include phosphorothioated cytosine-guanosine (CpG) oligonucleotides, a motif often seen in bacterial or viral DNA. (uci.edu)
  • Here we showed that in migrating MDA-MB-231 cells Rab40c regulates focal adhesion's number, size, and distribution. (life-science-alliance.org)
  • MATERIALS AND METHODS: The components of S&P extract were first detected using the liquid chromatography-tandem mass spectrometry (LC-MS/MS). The effects of S&P extract on the viability and migration ability of macrophages were detected using CCK8, LDH, adhesion and transwell assays. (bvsalud.org)
  • Podosomes are ring-shaped adhesions often found in fast-moving cells, such as macrophages. (cellmigration.org)
  • In this study, it was observed that the ion implantation stimulated the neural proliferation and the implantation of different ions on cell culture surfaces was essential to determine the effects of this technique on adhesion, proliferation, differentiation and apoptosis properties of cells in details. (omicsonline.org)
  • The resistance of cells on a biomaterial to compressive, tensile, or shear forces largely depends on the cell adhesion strength [ 8 ]. (alliedacademies.org)
  • 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)
  • For paxillin coprecipitation transiently transfected Chinese hamster ovary (CHO).K1 or HEK293A cells were replated about 10 μg/ml fibronectin for 60 min before control. (healthyguide.info)
  • GFP-Paxillin WT-expressing cells functioned basically the same as GFP control cells. (healthyguide.info)
  • Manifestation of GFP-PKL TripleYF raises cell protrusiveness much like cells expressing paxillin ΔLD4. (healthyguide.info)
  • We now report that DU145 human prostate cancer cells with reduced levels of PAK4 expression are unable to successfully migrate in response to HGF, have prominent actin stress fibres, and an increase in the size and number of focal adhesions. (silverchair.com)
  • These receptors are responsible for activating key pathways in cancer cells that lead to their proliferation and survival. (wisc.edu)
  • 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)
  • 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)
  • 1 integrin, coupled with one of its many partners, is thought to play a central role in focal adhesion formation. (ppbhg.org)
  • This study aimed to investigate the mechanical adhesion strength of the Connective Tissue Equivalents (CTEs) to the Ceria-stabilized Tetragonal Zirconia Polycrystal/Alumina (Ce-TZP/Al 2 O 3 ) surface. (alliedacademies.org)
  • Furthermore, the mechanical adhesion strength of CTEs to the disk surface was measured using the nano-scratch test. (alliedacademies.org)
  • This study provides the first evidence for the mechanical adhesion strength of CTEs to Ce-TZP/Al 2 O 3 and Ti surfaces. (alliedacademies.org)
  • Connective tissue equivalents, Mechanical adhesion strength, Nano-scratch test. (alliedacademies.org)
  • 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)
  • However, the mechanisms and specificity by which these LPA receptors mediate LPA actions are still poorly understood. (ntnu.edu.tw)
  • TRIP6 directly binds to the carboxyl-terminal tail of the LPA 2 receptor through its LIM domains. (ntnu.edu.tw)