• This family also includes Abl, Src, focal adhesion kinase and Janus kinase. (wikipedia.org)
  • Focal adhesion kinase (FAK) is a key integrator of integrin-mediated signals from the extracellular matrix to the cytoskeleton and downstream signaling molecules. (techscience.com)
  • Here, using different experimental approaches, especially designer receptor exclusively activated by designer drug (DREADD) chemogenetic technology, we found that sustained activation of G q -protein signaling impairs the functionality of striatal neurons and we unveil the precise molecular mechanism underlying this process: a phospholipase C/Ca 2+ /proline-rich tyrosine kinase 2/cJun N -terminal kinase pathway. (jneurosci.org)
  • Significant reductions in the phosphorylation of signaling molecules focal adhesion kinase, extracellular signal-regulated kinases 1 and 2, and v-Akt murine thymoma viral oncogene were observed in male MIPβ1KO islets when compared to controls. (oncotarget.com)
  • β1 integrin is the major β integrin subunit in pancreatic beta-cells and forms heterodimers with 12 α integrin subunits, which interact with components of the extracellular matrix (ECM) to control intracellular signaling via the focal adhesion kinase (FAK) and extracellular signal related kinase 1 and 2 (ERK1/2) pathways [ 4 ]. (oncotarget.com)
  • The integrin tails have no intrinsic kinase activity but rather serve as a site for the docking of various kinases and related adaptor proteins that comprise focal adhesions. (thno.org)
  • Bacterial IbeA interacts with endothelial Caspr1 to trigger intracellular focal adhesion kinase activation, leading to E. coli internalization into the brain endothelial cells. (microbialcell.com)
  • In the present study we identify the focal adhesion-associated proteins p130Cas, Pyk2, and paxillin as novel members of the tyrosine kinase signaling pathway downstream of CD36 and show that assembly of this complex is essential for microglial migration. (neuroprobe.com)
  • Fyn, a Src kinase known to interact with CD36, co-precipitates with p130Cas and is an essential upstream intermediate in the signaling pathways leading to phosphorylation of the p130Cas substrate domain. (neuroprobe.com)
  • Furthermore, the p130Cas-interacting kinase Pyk2 and the cytoskeletal adapter protein paxillin also demonstrate CD36-dependent phosphorylation, identifying these focal adhesion molecules as additional members of this β-amyloid signaling cascade. (neuroprobe.com)
  • Our results demonstrate that cytoglobin expression is correlated with a more quiescent phenotype of stellate cells in culture and that cytoglobin is regulated by the extracellular matrix through integrin signalling dependent on activation of focal adhesion kinase. (biomedcentral.com)
  • Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. (wikipedia.org)
  • Lysophosphatidic acid (LPA) is a ubiquitous lysophospholipid and one of the main membrane-derived lipid signaling molecules. (hindawi.com)
  • Although previous studies have identified different chemotropic and adhesion molecules that influence axonal development, the molecular mechanism by which these signals control the cytoskeleton remains poorly understood. (biologists.com)
  • Integrins are heterodimeric, transmembrane receptors that function as mechanosensors, adhesion molecules and signal transduction platforms in a multitude of biological processes. (thno.org)
  • Disruptions in these signaling pathways often have implications in the formation of a variety of cancers. (wikipedia.org)
  • Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane, where it phosphorylates tyrosine residues on key targets involved in a variety of different signaling pathways. (wikipedia.org)
  • Knowing which pathways involve Fyn will provide key insight for the development of potential pharmacologic agents to attenuate this uncontrolled signaling. (wikipedia.org)
  • LPA activates at least six G-coupled protein receptors (LPA 1-6 ) stimulating different signaling pathways through heterotrimeric G proteins such as G i/0 , G 12/13 , G q/11 , and G s . (hindawi.com)
  • 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)
  • By modulating the activity of these proteins or their downstream signaling pathways, we aim to mitigate the cellular responses to abnormal mechanical forces, potentially slowing the progression of neurodegenerative diseases and offering new avenues for treatment and prevention. (shubhasis-haldar-cmt.com)
  • Moreover, engagement of this intracellular signaling route was functionally active in the mouse dorsal striatum in vivo , as proven by the disruption of neuronal integrity and behavioral tasks. (jneurosci.org)
  • The biodirectional nature of integrin mediated signaling allows both extra- and intracellular cues to regulate activation [ 4 ] (Fig. 1 ). (thno.org)
  • Intracellular signaling events that converge on the cytoplasmic domain of integrin tails are also capable of activating the high affinity state. (thno.org)
  • Intracellular signals that result in integrin activation are referred to as 'inside-out' signaling events. (thno.org)
  • Integrin ligation via cell-to-cell and cell-to-matrix contacts transduces intracellular signaling events in a process called 'outside-in' signaling (Fig. 2 ). (thno.org)
  • FAK is activated by phosphorylation at specific tyrosine residues, which then stimulate downstream signaling including the ERK1/2 pathway, leading to a variety of cellular responses. (techscience.com)
  • Interaction with ECM is a major driver of HSC morphology [ 11 ], and signal transduction from integrin activation occurs at least partly through aggregation and subsequent activation of focal adhesion kinases (FAKs) by autophosphorylation of tyrosine 397 (Y397). (biomedcentral.com)
  • Extracellular factors that influence integrin activation are ligand binding, divalent cation concentration, chemokine signaling and mechanical stress. (thno.org)
  • Focal adhesions are multi-protein complexes that connect the cell's cytoskeleton to the extracellular matrix, allowing the cell to sense and respond to mechanical cues from its environment. (shubhasis-haldar-cmt.com)
  • Together, these data are the first to identify the signaling cascade that directly links CD36 to the actin cytoskeleton and, thus, implicates it in diverse processes such as cellular migration, adhesion, and phagocytosis. (neuroprobe.com)
  • Cell migration is controlled by a force-driven cellular brake system called focal adhesion (FA), a multiprotein assembly of almost 200 proteins. (shubhasis-haldar-cmt.com)
  • Mechanosensitive proteins play a crucial role in focal adhesion-mediated neurodegeneration, a process that involves the breakdown of nerve cells in the central nervous system due to abnormal mechanical forces acting on the cells. (shubhasis-haldar-cmt.com)
  • In the context of neurodegeneration, these mechanosensitive proteins become instrumental in transmitting and translating mechanical signals, ultimately contributing to neuronal damage. (shubhasis-haldar-cmt.com)
  • Understanding the role of mechanosensitive proteins in focal adhesion-mediated neurodegeneration is critical for developing targeted therapeutic interventions. (shubhasis-haldar-cmt.com)
  • Mechanical forces are transduced into biochemical signals by specialized proteins. (nature.com)
  • Fyn is a 59-kDa member of the Src family of kinases typically associated with T-cell and neuronal signaling in development and normal cell physiology. (wikipedia.org)
  • Fyn is a protein, present in the signaling pathway of integrins, which activates ras. (wikipedia.org)
  • Our results demonstrate that FAK signaling emanating from Y397, Y925, and to a lesser extent Y576/7, but not from Y861, controls osteogenic differentiation through an ERK1/2 pathway, as measured by expression levels of key osteogenesis marker genes and subsequent matrix mineralization. (techscience.com)
  • To analyze this effect anatomically, we manipulated G q -protein-dependent signaling selectively in neurons belonging to the direct or indirect striatal pathway. (jneurosci.org)
  • The outcome of LPA signaling is dependent on cellular context and impacts on biological processes such as wound healing, differentiation, neurogenesis, and survival, to name a few [ 4 ]. (hindawi.com)
  • Whereas the G s /G i -protein-dependent tuning of striatal neurons is fairly well known, the precise impact and underlying mechanism of G q -protein-dependent signals remain poorly understood. (jneurosci.org)
  • The β-tail is the primary docking site in the formation of focal adhesions, but the alpha tail in some cases may also serve as a signaling scaffold for calcium dependent signaling events. (thno.org)
  • It is known that ATX-LPA signaling increases during wound healing, and both are produced and detected in blister fluids, where they mediate platelet aggregation and skin reepithelization [ 8 ]. (hindawi.com)
  • Fyn is located downstream of several cell surface receptors, commonly associated with neuronal development and T-cell signaling. (wikipedia.org)
  • 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)
  • When fyn is activated it causes downstream activation of molecular signals that drive processes crucial to growth and motility of cells. (wikipedia.org)
  • Focal adhesions act as molecular clutches that provide grip to the substrate for the lamellipodium to protrude forward during motility. (mechanobio.info)
  • Signals emanating from focal adhesions have been shown to promote survival, differentiation and proliferation [ 5 ]. (thno.org)
  • To minimize discrepancies and inconsistencies, and allow comparison of data generated in different laboratories, the International Society of Cellular Therapy (ISCT) has provided guidelines for the definition of MSCs based on (a) their plastic adhesion properties, (b) immunophenotype, and (c) multi-potent differentiation potential (Bourin et al. (neurogelenmarche-usa.org)
  • Fyn also appears to play an important role in fertilization including in the rapid Inositol trisphosphate-mediated calcium signaling which occurs when oocyte and sperm interact. (wikipedia.org)
  • There are numerous downstream signalling targets of FAK with many of the effects ultimately mediated by changes in gene expression [ 11 - 13 ]. (biomedcentral.com)
  • In vitro assays confirmed that the two compounds, to varying extents, inhibited RA-FLS proliferation, migration, invasion, and NF-κB signaling. (frontiersin.org)
  • The pattern recognition receptor CD36 initiates a signaling cascade that promotes microglial activation and recruitment to β-amyloid deposits in the brain. (neuroprobe.com)
  • The complete integumentary organ system (IOS) regeneration and scarless wound healing mechanism, which occurs in specific species, body sites and developmental stages, clearly shows that mechanical stress signals and immune responses play important roles in determining the wound healing mode. (mdpi.com)
  • In the absence of integrin ligation, these processes are abrogated therefore pharmacological inhibition of integrin ligation is of great interest for the therapy of numerous diseases resulting from abberant integrin mediated signaling. (thno.org)
  • Due to their permeability to Ca 2+ and other cations, Piezo channel activity generates chemical as well as electrical signals in response to mechanical stimuli, allowing them to regulate a wide variety of cellular processes. (nature.com)
  • The protrusions of the cell edge are shown as green arrows corresponding to points of adhesion maturation (panels 3 and 4). (mechanobio.info)
  • We employ a range of techniques, such as covalent magnetic tweezers to study mechanochemical signaling, microfabricated substrates to apply controlled mechanical forces, and live-cell imaging to observe cellular responses in real time. (shubhasis-haldar-cmt.com)
  • During this process, ATX-LPA signaling induces production of proinflammatory cytokines. (hindawi.com)
  • Integrin mediated cellular adhesion is dynamic process that is both indicative of and influenced by cell status. (thno.org)
  • The establishment of neural circuits depends on the ability of axonal growth cones to sense their surrounding environment en route to their target. (biologists.com)
  • Many ongoing studies aim to understand ATX-LPA axis signaling in cancer and its potential as a therapeutic target. (hindawi.com)
  • Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration. (nature.com)
  • Panel 4 shows sliding of adhesion and hence slight retraction of the respective section of the cell edge compared to panel 3. (mechanobio.info)