A microfilament protein that interacts with F-ACTIN and regulates cortical actin assembly and organization. It is also an SH3 DOMAIN containing phosphoprotein, and it mediates tyrosine PHOSPHORYLATION based SIGNAL TRANSDUCTION by PROTO-ONCOGENE PROTEIN PP60(C-SRC).
Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.
A component of the Arp2-3 complex that is related in sequence and structure to ACTIN and that binds ATP. It is expressed at higher levels than ARP2 PROTEIN and does not contain a PROFILIN binding domain.
A PROFILIN binding domain protein that is part of the Arp2-3 complex. It is related in sequence and structure to ACTIN and binds ATP.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
A complex of seven proteins including ARP2 PROTEIN and ARP3 PROTEIN that plays an essential role in maintenance and assembly of the CYTOSKELETON. Arp2-3 complex binds WASP PROTEIN and existing ACTIN FILAMENTS, and it nucleates the formation of new branch point filaments.
A member of the Wiskott-Aldrich syndrome protein family that is found at high levels in NERVE CELLS. It interacts with GRB2 ADAPTOR PROTEIN and with CDC42 PROTEIN.
Specialized structures of the cell that extend the cell membrane and project out from the cell surface.
A dynamic actin-rich extension of the surface of an animal cell used for locomotion or prehension of food.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
A subtype of dynamin found ubiquitously expressed in a variety of tissues.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments.
A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin.
A MARVEL domain-containing protein found in the presynaptic vesicles of NEURONS and NEUROENDOCRINE CELLS. It is commonly used as an immunocytochemical marker for neuroendocrine differentiation.
Compounds that contain the Cl(=O)(=O)(=O)O- structure. Included under this heading is perchloric acid and the salts and ester forms of perchlorate.
A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in MOLECULAR GENETICS to detect the presence of a complementary sequence by NUCLEIC ACID HYBRIDIZATION.
Hard, amorphous, brittle, inorganic, usually transparent, polymerous silicate of basic oxides, usually potassium or sodium. It is used in the form of hard sheets, vessels, tubing, fibers, ceramics, beads, etc.
Compounds that contain three methine groups. They are frequently used as cationic dyes used for differential staining of biological materials.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
The portion of an interactive computer program that issues messages to and receives commands from a user.
Sequential operating programs and data which instruct the functioning of a digital computer.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.
Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.
Antibodies produced by a single clone of cells.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
An encapsulated lymphatic organ through which venous blood filters.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)
A genus in the family ORTHOMYXOVIRIDAE causing influenza and other diseases in humans and animals. It contains many strains as well as antigenic subtypes of the integral membrane proteins hemagglutinin (HEMAGGLUTININS) and NEURAMINIDASE. The type species is INFLUENZA A VIRUS.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Proteins prepared by recombinant DNA technology.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Chemical reaction in which monomeric components are combined to form POLYMERS (e.g., POLYMETHYLMETHACRYLATE).
Activities performed to identify concepts and aspects of published information and research reports.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Use of sophisticated analysis tools to sort through, organize, examine, and combine large sets of information.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.
Adherence of cells to surfaces or to other cells.
Movement of tethered, spherical LEUKOCYTES along the endothelial surface of the microvasculature. The tethering and rolling involves interaction with SELECTINS and other adhesion molecules in both the ENDOTHELIUM and leukocyte. The rolling leukocyte then becomes activated by CHEMOKINES, flattens out, and firmly adheres to the endothelial surface in preparation for transmigration through the interendothelial cell junction. (From Abbas, Cellular and Molecular Immunology, 3rd ed)
The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.

Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway. (1/335)

Lymphocyte extravasation into the brain is mediated largely by the Ig superfamily molecule ICAM-1. Several lines of evidence indicate that at the tight vascular barriers of the central nervous system (CNS), endothelial cell (EC) ICAM-1 not only acts as a docking molecule for circulating lymphocytes, but is also involved in transducing signals to the EC. In this paper, we examine the signaling pathways in brain EC following Ab ligation of endothelial ICAM-1, which mimics adhesion of lymphocytes to CNS endothelia. ICAM-1 cross-linking results in a reorganization of the endothelial actin cytoskeleton to form stress fibers and activation of the small guanosine triphosphate (GTP)-binding protein Rho. ICAM-1-stimulated tyrosine phosphorylation of the actin-associated molecule cortactin and ICAM-1-mediated, Ag/IL-2-stimulated T lymphocyte migration through EC monolayers were inhibited following pretreatment of EC with cytochalasin D. Pretreatment of EC with C3 transferase, a specific inhibitor of Rho proteins, significantly inhibited the transmonolayer migration of T lymphocytes, endothelial Rho-GTP loading, and endothelial actin reorganization, without affecting either lymphocyte adhesion to EC or cortactin phosphorylation. These data show that brain vascular EC are actively involved in facilitating T lymphocyte migration through the tight blood-brain barrier of the CNS and that this process involves ICAM-1-stimulated rearrangement of the endothelial actin cytoskeleton and functional EC Rho proteins.  (+info)

Cell shrinkage regulates Src kinases and induces tyrosine phosphorylation of cortactin, independent of the osmotic regulation of Na+/H+ exchangers. (2/335)

The signaling pathways by which cell volume regulates ion transporters, e.g. Na+/H+ exchangers (NHEs), and affects cytoskeletal organization are poorly understood. We have previously shown that shrinkage induces tyrosine phosphorylation in CHO cells, predominantly in an 85-kDa band. To identify volume-sensitive kinases and their substrates, we investigated the effect of hypertonicity on members of the Src kinase family. Hyperosmolarity stimulated Fyn and inhibited Src. Fyn activation was also observed in nystatin-permeabilized cells, where shrinkage cannot induce intracellular alkalinization. In contrast, osmotic inhibition of Src was prevented by permeabilization or by inhibiting NHE-1. PP1, a selective Src family inhibitor, strongly reduced the hypertonicity-induced tyrosine phosphorylation. We identified one of the major targets of the osmotic stress-elicited phosphorylation as cortactin, an 85-kDa actin-binding protein and well known Src family substrate. Cortactin phosphorylation was triggered by shrinkage and not by changes in osmolarity or pHi and was abrogated by PP1. Hyperosmotic cortactin phosphorylation was reduced in Fyn-deficient fibroblasts but remained intact in Src-deficient fibroblasts. To address the potential role of the Src family in the osmotic regulation of NHEs, we used PP1. The drug affected neither the hyperosmotic stimulation of NHE-1 nor the inhibition of NHE-3. Thus, members of the Src family are volume-sensitive enzymes that may participate in the shrinkage-related reorganization of the cytoskeleton but are probably not responsible for the osmotic regulation of NHE.  (+info)

Regulation of endothelial cell myosin light chain kinase by Rho, cortactin, and p60(src). (3/335)

Inflammatory diseases of the lung are characterized by increases in vascular permeability and enhanced leukocyte infiltration, reflecting compromise of the endothelial cell (EC) barrier. We examined potential molecular mechanisms that underlie these alterations and assessed the effects of diperoxovanadate (DPV), a potent tyrosine kinase activator and phosphatase inhibitor, on EC contractile events. Confocal immunofluorescent microscopy confirmed dramatic increases in stress-fiber formation and colocalization of EC myosin light chain (MLC) kinase (MLCK) with the actin cytoskeleton, findings consistent with activation of the endothelial contractile apparatus. DPV produced significant time-dependent increases in MLC phosphorylation that were significantly attenuated but not abolished by EC MLCK inhibition with KT-5926. Pretreatment with the Rho GTPase-inhibitory C3 exotoxin completely abolished DPV-induced MLC phosphorylation, consistent with Rho-mediated MLC phosphatase inhibition and novel regulation of EC MLCK activity. Immunoprecipitation of EC MLCK after DPV challenge revealed dramatic time-dependent tyrosine phosphorylation of the kinase in association with increased MLCK activity and a stable association of MLCK with the p85 actin-binding protein cortactin and p60(src). Translocation of immunoreactive cortactin from the cytosol to the cytoskeleton was noted after DPV in concert with cortactin tyrosine phosphorylation. These studies indicate that DPV activates the endothelial contractile apparatus in a Rho GTPase-dependent fashion and suggests that p60(src)-induced tyrosine phosphorylation of MLCK and cortactin may be important features of contractile complex assembly.  (+info)

Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. (4/335)

NMDA receptors are linked to intracellular cytoskeletal and signaling molecules via the PSD-95 protein complex. We report a novel family of postsynaptic density (PSD) proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank/GKAP/PSD-95 assembles in heterologous cells and can be coimmunoprecipitated from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton.  (+info)

Tyrosine phosphorylation of cortactin associated with Syk accompanies thromboxane analogue-induced platelet shape change. (5/335)

Thromboxane A(2) (TxA(2)) is a potent vasoconstrictor and platelet agonist. Pharmacological studies have defined two classes of thromboxane receptors (TPs) in human platelets; sites that bind the agonist 1S-(1,2(5Z),3-(1E,3S),4)-7- 3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo-2.2. 1-heptan-2-yl-5-heptenoic acid (I-BOP) with high affinity support platelet shape change, whereas low affinity sites that bind irreversibly the antagonist GR 32191 transduce platelet aggregation. As the mechanisms of signal transduction involved in platelet aggregation begin to be elucidated, few results concern those involved in platelet shape change, which is independent of the engagement of GPIIb/IIIa. To elucidate the respective role of the two classes of pharmacological binding sites of TPs in shape change, platelets were incubated with I-BOP at low concentrations or stimulated by I-BOP at high concentrations after pretreatment with GR 32191 or activated with low concentrations of 8-epi-prostaglandin F(2)alpha. Under these three conditions, there is a rapid stimulation of protein tyrosine phosphorylation of the 80/85-kDa doublet identified as the cytoskeletal protein cortactin. Tyrosine phosphorylation of cortactin is kinetically correlated with the occurrence of shape change. These biochemical and morphological events are both inhibited by SQ 29548, a TP antagonist, indicating the specificity of the signal. Since tyrosine kinase Syk was activated early during platelet activation, we examined the possibility that cortactin is a potential substrate of Syk in TxA(2)-induced platelet shape change. p72 Syk phosphorylation and kinase activity took place during the period when platelets were changing shape upon low concentrations of I-BOP stimulation. Furthermore, cortactin was associated with Syk, and this association increases along with the level of phosphorylation. These data suggest a novel pathway for a G protein-coupled TxA(2) high affinity receptor to the protein-tyrosine kinase Syk, which is associated with cortactin in the very early steps of platelet activation.  (+info)

An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation. (6/335)

Invasive breast cancer cells have the ability to extend membrane protrusions, invadopodia, into the extracellular matrix (ECM). These structures are associated with sites of active matrix degradation. The amount of matrix degradation associated with the activity of these membrane protrusions has been shown to directly correlate with invasive potential. We demonstrate here that microinjection of polyclonal anti-cortactin antibodies blocks matrix degradation at invadopodia supporting the hypothesis that cortactin has a direct role in invasive behavior. MDA-MB-231, invasive breast cancer cells were sheared from the surface of a gelatin matrix to isolate invadopodia. Cortactin, paxillin and protein kinase C (PKC) mu, a serine kinase, were co-immunoprecipitated as a complex from invadopodia-enriched membranes. We confirmed the subcellular distribution of these proteins by immunolocalization and Western blotting. We also determined that, in contrast to its presence in invasive cells, this complex of proteins was not detected in lysates from non-invasive cells that do not form invadopodia. Taken together, these data suggest that the formation of this cortactin-containing complex correlates with cellular invasiveness. We hypothesize that this complex of molecules has a role in the formation and function of invadopodia during cellular invasion.  (+info)

Signaling pathways and structural domains required for phosphorylation of EMS1/cortactin. (7/335)

The structural characteristics of EMS1 (human cortactin) suggest that it may link signaling events to reorganization of the actin cytoskeleton. Interestingly, the EMS1 gene is commonly amplified and overexpressed in several human cancers, which may alter their invasive or metastatic properties. An 80 to 85-kDa mobility shift of EMS1 correlates with an alteration in subcellular distribution and is likely to represent an important regulatory event. In HEK 293 cells, epidermal growth factor treatment or cell detachment induced this shift, and this was blocked by the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059. Furthermore, expression of a constitutively active form of MEK induced the shift, indicating that MEK activation was both sufficient and necessary for this modification. The epidermal growth factor-induced shift correlated with increased phosphorylation on serine and threonine residues of the same tryptic phosphopeptides detected under basal conditions. Deletion of the helical-proline-rich region of the protein blocked the mobility shift and EMS1 phosphorylation. In vitro kinase assays demonstrated that the extracellular signal-regulated kinases represent candidate kinases for this region, although other MEK-regulated enzymes must also participate. These data identify MEK as an important intermediate involved in EMS1 phosphorylation and highlight the helical-proline-rich region as a key regulatory domain.  (+info)

Synapse structure: glutamate receptors connected by the shanks. (8/335)

A family of proteins has been identified whose members, the Shanks, physically link two major receptor complexes at excitatory synapses - NMDA receptors and metabotropic glutamate receptors.  (+info)

The CTTN gene (formerly designated EMS1), encodes cortactin, a key regulator of dynamic actin networks. Both CTTN and CCND1, the latter encoding the cell cycle regulator cyclin D1, reside at chromosomal locus 11q13, a region commonly amplified in breast cancers and head and neck squamous cell carcinoma (HNSCC). Previously, we identified a novel role for cortactin in cancer cells, whereby cortactin overexpression attenuated ligand-induced down-regulation of the epidermal growth factor (EGF) receptor (EGFR), leading to sustained signaling. However, how this affected growth factor-induced cellular responses was unclear. Here, by modulation of cortactin expression in a panel of HNSCC cell lines, we show that cortactin overexpression enhances serum- and EGF-stimulated proliferation under both anchorage-dependent and anchorage-independent conditions and also increases resistance to anoikis (detachment-induced apoptosis). These effects are associated with increased activation of extracellular signal-regulated
Dynamic regulation of cell-cell adhesion by the coordinated formation and dissolution of E-cadherin-based adherens junctions is crucial for tissue homeostasis. The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. Here, we were interested to study the broader functional interactions of cortactin in adhesion complexes. In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1;also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution. Two new S298-phosphorylation-dependent interactions were also identified, namely, that phosphorylation of cortactin decreases its interaction with beta-catenin and the actin-binding protein vinculin. In addition, binding of vinculin to beta-catenin, as well as linkage of vinculin to F-actin, are also significantly compromised upon ...
We present a molecular dissection of the functional domains of cortactin relevant for invadopodia formation and function. In addition, through the expression of cortactin forms mutated in the residues previously found to be phosphorylated in vitro, we suggest the involvement of different kinases in the control of the ECM degradation machinery through the regulation of cortactin phosphorylation.. The overexpression of mutant or deleted forms of cortactin that are unable to bind the Arp2/3 complex, induces a substantial decrease in the ability of the cells to form invadopodia and hence degrade the ECM. In addition, the SH3 domain of cortactin, known to bind a number of relevant proteins such as N-WASP and dynamin 2, is also essential for invadopodia formation and ECM degradation. This is at variance with a recent report suggesting that the cortactin N-terminus is not required for invadopodia formation (Webb et al., 2007). A possible explanation is that the study was based on constitutively active ...
Invasive carcinoma cells use specialized actin polymerization-driven protrusions called invadopodia to degrade and possibly invade through the extracellular matrix (ECM) during metastasis. Phosphorylation of the invadopodium protein cortactin is a master switch that activates invadopodium maturation and function. Cortactin was originally identified as a hyperphosphorylated protein in v-Src-transformed cells, but the kinase or kinases that are directly responsible for cortactin phosphorylation in invadopodia remain unknown. In this study, we provide evidence that the Abl-related nonreceptor tyrosine kinase Arg mediates epidermal growth factor (EGF)-induced cortactin phosphorylation, triggering actin polymerization in invadopodia, ECM degradation, and matrix proteolysis-dependent tumor cell invasion. Both Src and Arg localize to invadopodia and are required for EGF-induced actin polymerization. Notably, Arg overexpression in Src knockdown cells can partially rescue actin polymerization in ...
The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to amplification of the encoding gene (CTTN). While cortactin overexpression enhances invasive potential, recent research indicates that it also promotes cell proliferation, but how cortactin regulates the cell cycle machinery is unclear. In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. Cortactin regulated expression of p21(WAF1/Cip1) and p27(Kip1) at the transcriptional and posttranscriptional levels, respectively. The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) ...
Proper regulation of cell morphogenesis and migration by adhesion and growth-factor receptors requires Abl-family tyrosine kinases [1-3]. Several substrates of Abl-family kinase have been identified, but they are unlikely to mediate all of the downstream actions of these kinases on cytoskeletal stru …
Analyzing cortactin-deficient mice, we show for the first time that this actin-remodeling protein is required in endothelial cells, not in neutrophils, for optimal efficiency of neutrophil recruitment to inflamed tissue. Loss of cortactin caused an increase in rolling velocity and a decrease of neutrophil adhesion to the vessel wall. Thus, endothelial cortactin is required for slowing down rolling neutrophils and for firm adhesion to the vessel wall. Interestingly, cortactin was not required for the support of selectin-mediated rolling but for the slowing down of rolling mediated by β2-integrins and their ligands. In addition, formation of ICAM-1-containing clusters was disturbed, providing a possible explanation for the decreased numbers of neutrophils adhering to the vessel wall. Searching for a mechanism for this defect, we found that cortactin deficiency blocked the activation of RhoG triggered by ICAM-1 engagement, and CA-RhoG partially restored ICAM-1 clustering and neutrophil ...
The endocytic protein dynamin participates in the formation of actin-based membrane protrusions such as podosomes, pseudopodia, and invadopodia, which facilitate cancer cell migration, invasion, and metastasis. However, the role of dynamin in the formation of actin-based membrane protrusions at the leading edge of cancer cells is unclear. In this study, we demonstrate that the ubiquitously expressed dynamin 2 isoform facilitates cell migration by stabilizing F-actin bundles in filopodia of the lung cancer cell line H1299. Pharmacological inhibition of dynamin 2 decreased cell migration and filopodial formation. Furthermore, dynamin 2 and cortactin mostly colocalized along F-actin bundles in filopodia of serum-stimulated H1299 cells by immunofluorescent and immunoelectron microscopy. Knockdown of dynamin 2 or cortactin inhibited the formation of filopodia in serum-stimulated H1299 cells, concomitant with a loss of F-actin bundles. Expression of wild-type cortactin rescued the punctate-like ...
Invadopodia are actin-enriched cell protrusions that cancer cells use to degrade the extracellular matrix (ECM), which then allows for cancer cell invasion, and these processes require the binding of tyrosine-phosphorylated cortactin, an actin binding protein, with the Rho-family GTPase guanine nucleotide exchange factor (GEF) Vav2, which results in recruitment of Vav2 to invadopodia where Vav2 mediates invadopodial maturation and function through re-arrangement of the actin cytoskeleton, likely through activation of the Rac3 GTPase.
Shop a large selection of products and learn more about Cortactin Rabbit anti-Mouse, Rat, Polyclonal, Novus Biologicals:: 100 µg; Unconjugated.
Cortactin兔单克隆抗体[EP1922Y](ab81208)可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC, Flow Cyt, ICC/IF实验严格验证,被3篇文献引用并得到1个独立的用户反馈。
F-actin helps mitochondria divide by polymerizing on the organelles, Li et al. show.. The GTPase Drp1 forms spirals around mitochondria to cut the organelles in two. Studies suggest that actin also has a role in mitochondrial division and recruitment of Drp1. The mechanisms, however, remain unclear.. Li et al. found that F-actin polymerizes on the outer mitochondrial membrane in cultured cells but doesnt extend into the organelles. When the researchers spurred mitochondria to divide by putting them under stress, F-actin amassed on the organelles. However, latrunculin B, which prevents actin polymerization, curtailed this accumulation. Actin therefore gathers on mitochondria when they are ready to split.. The proteins cortactin and cofilin and the Arp2/3 complex-all of which spur actin to branch- also collect on mitochondria, Li et al. found. Depleting any of these factors led to extra-long mitochondria but didnt alter the rate of organelle fusion, suggesting that actin branching promotes ...
Sigma-Aldrich offers abstracts and full-text articles by [Jagadeesh Janjanam, Giri Kumar Chandaka, Sivareddy Kotla, Gadiparthi N Rao].
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Our research encompasses basic cell biology of tumor cell invasion, focusing on two tyrosine kinases, c-Src and Syk, with opposing roles in cancer metastasis. A major focus is invadopodia, the cell surface membrane protrusions formed during tumor cell invasion, and their role in invasion and metastasis. We use cortactin, a Src substrate, and MT1-MMP, an extracellular matrix-degrading, membrane protein, to identify and study the formation of invadopodia and acquisition of proteolytic activity. High resolution light and electron microscopy techniques are used to identify these structures and examine the membrane-associated signal transduction events that occur in conjunction with the formation of invadopodia. In vitro and in vivo assays are used to measure the consequent matrix adhesion, proteolysis and phagocytosis that are mediated by invadopodia. We also focus on determining the mechanism of breast cancer tumor suppression by the Syk tyrosine kinase. Utilizing mouse model systems, 3D culture ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Knockout Tested Rabbit recombinant monoclonal Cortactin antibody [EP1922Y]. Validated in WB, IP, IHC, Flow Cyt, ICC/IF and tested in Mouse, Rat, Human. Cited in 16 publication(s). Independently…
Esophageal cancer is an aggressive human malignancy with rising incidence in the developed world. The vascular endothelial growth factor VEGF-C makes crucial contributions to esophageal cancer progression that are not well understood. Here we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin (CTTN), a regulator of the cortical actin cytoskeleton. Upregulation of CTTN expression by VEGF-C enhanced the invasive propertis of esophageal squamous cell carcinoma (ESCC) in vitro and tumor metastasis in vivo. Mechanistic investigations showed that VEGF-C increased CTTN expression by downregulating Dicer-mediated maturation of miR-326, thereby relieving the suppressive effect of miR-326 on CTTN expression. Clinically, expression of Dicer and miR-326 correlated with poor prognosis in esophageal cancer patients. Our findings offer insights into how VEGF-C enhances the robust invasive and metastatic properties of esophageal cancer, which ...
Ammer, A.G., and Weed, S.A. (2008). Cortactin branches out: roles in regulating protrusive actin dynamics. Cell Motil. Cytoskeleton 65: 687-707. PubMed Citation: 18615630 Arnaud, L., Ballif, B.A., Forster, E., and Cooper, J.A. (2003). Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development. Curr. Biol. 13: 9-17. 12526739 Baba, K., et al. (1999). The Drosophila Brutons tyrosine kinase (Btk) homolog is required for adult Survival and male genital formation. Mol. Cell. Biol. 19: 4405-4413. PubMed Citation: 10330180 Bei, Y., et al. (2002). SRC-1 and Wnt signaling act together to specify endoderm and to control cleavage orientation in early C. elegans embryos. Dev. Cell 3: 113-125. 12110172 Bershteyn, M., Atwood, S. X., Woo, W. M., Li, M. and Oro, A. E. (2010). MIM and cortactin antagonism regulates ciliogenesis and hedgehog signaling. Dev. Cell 19(2): 270-83. PubMed Citation: 20708589 Billuart, P., Winter, C. G., Maresh, A., Zhao, X. and Luo, L. (2001). Regulating axon ...
Immunocytochemistry for confocal microscopy. Sections were blocked in 20% normal donkey serum (NDS; Jackson ImmunoResearch, West Grove, PA) in 0.05 m PBS, pH 7.4, then incubated in various combinations of primary antibodies for cortactin, α-actinin, synaptophysin, and VGLUT1 in PBS containing 2% NDS overnight at room temperature. After several washes, sections were incubated in secondary antibodies (anti-rabbit Cy3 for cortactin, anti-mouse FITC for synaptophysin and VGLUT1). Alexa Fluor-488 conjugated to phalloidin (Molecular Probes, Eugene, OR) was used for visualization of F-actin (Allison et al., 1998). For visualization of cell processes, we used the lipophilic dye 3,3′-dioctadecyloxacarbocyanidine perchlorate (DiO; Molecular Probes), which infiltrates the plasma membrane, labeling even the finest neuronal processes (for details, see Burette et al., 2002). After several washes, sections were mounted on glass slides, coverslipped in Vectashield (Vector Laboratories, Burlingame, CA) and ...
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TY - JOUR. T1 - CD44 regulates hepatocyte growth factor-mediated vascular integrity. T2 - Role of c-Met, Tiam1/Rac1, dynamin 2, and cortactin. AU - Singleton, Patrick A.. AU - Salgia, Ravi. AU - Moreno-Vinasco, Liliana. AU - Moitra, Jaideep. AU - Sammani, Saad. AU - Mirzapoiazova, Tamara. AU - Garcia, Joe GN. PY - 2007/10/19. Y1 - 2007/10/19. N2 - The preservation of vascular endothelial cell (EC) barrier integrity is critical to normal vessel homeostasis, with barrier dysfunction being a feature of inflammation, tumor angiogenesis, atherosclerosis, and acute lung injury. Therefore, agents that preserve or restore vascular integrity have important therapeutic implications. In this study, we explored the regulation of hepatocyte growth factor (HGF)-mediated enhancement of EC barrier function via CD44 isoforms. We observed that HGF promoted c-Met association with CD44v10 and recruitment of c-Met into caveolin-enriched microdomains (CEM) containing CD44s (standard form). Treatment of EC with ...
This protein protein interaction antibody pair set comes with two antibodies to detect the protein-protein interaction, one against the CASP3 protein, and the other against the CTTN protein for use in in situ Proximity Ligation Assay. See Publication Reference below. (DI0143) - Products - Abnova
Complete information for COTL1P1 gene (Pseudogene), Coactosin-Like F-Actin Binding Protein 1 Pseudogene 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Purified Recombinant Mouse CTTNBP2NL Protein from Creative Biomart. Recombinant Mouse CTTNBP2NL Protein can be used for research.
Shigella flexneri causes bacillary dysentery in humans by invading epithelial cells of the colon. Cell invasion occurs via bacterium-directed phagocytosis, a
Previous studies have suggested that N-syndecan regulates cell motility by binding to ECM-associated ligands like HB-GAM (for review see Rauvala et al., 2000). HB-GAM strongly promotes the haptotactic migration of forebrain cells, and the N-syndecan knockout cells fail completely to follow HB-GAM in vitro. The defective c-Src phosphorylation in the knockout cells is very likely associated with this failure. This interpretation is compatible with the finding that the cytosolic tail of N-syndecan binds a protein complex containing a PDZ domain protein calcium/CaM-dependent serine protein kinase (CASK), cortactin, and Fyn and Src kinases (Kinnunen et al., 1998b; Hsueh and Sheng, 1999; Lauri et al., 1999).. According to our findings, N-syndecan is important for the general migratory behavior of the forebrain cells. We demonstrate this by using EGFR-induced scatter behavior in forebrain cells as a test tool. Increasing EGFR activity in neural progenitor cells induces and promotes neural ...
The formation of cadherin-mediated cell-cell junctions is accompanied by a profound remodeling of the actin cytoskeleton. The Arp2/3 complex and its activator cortactin drive the assembly of branching actin-filament arrays, and formin-1 promotes the nucleation of non-branching actin filaments. Recru …
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that is a member of the Shank family of synaptic proteins that may function as molecular scaffolds in the postsynaptic density of excitatory synapses. Shank proteins contain multiple domains for protein-protein interaction, including ankyrin repeats, and an SH3 domain. This particular family member contains a PDZ domain, a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. The alternative splicing demonstrated in Shank genes has been suggested as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the postsynaptic densities of the adult and developing brain. Alterations in the encoded protein may be associated with susceptibility to autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014 ...
Local actin filament formation powers the development of the signal-receiving arbor of neurons. In this study, Izadi et al. demonstrate that Cobl-like, which bears only a single WH2 domain, mediates dendritic branching by coordinating with the F-actin-binding protein Abp1 in a Ca2+/CaM-controlled manner to control actin dynamics. ...
Local actin filament formation powers the development of the signal-receiving arbor of neurons. In this study, Izadi et al. demonstrate that Cobl-like, which bears only a single WH2 domain, mediates dendritic branching by coordinating with the F-actin-binding protein Abp1 in a Ca2+/CaM-controlled manner to control actin dynamics. ...
From NCBI Gene:. This gene encodes an intracellular F-actin binding protein. The protein is expressed in lymphocytes, neutrophils, macrophages, and endothelium and may regulate neutrophil motility, adhesion to fibrinogen matrix proteins, and transendothelial migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]. From UniProt: ...
AFAP1L2 overexpression lysate, 0.1 mg. Transient overexpression lysate of actin filament associated protein 1-like 2 (AFAP1L2), transcript variant 2
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Invadopodia facilitate cancer cell migration by breaking down the extracellular matrix that normally keeps cells in place. In previous research, Dr. Courtneidge discovered that Tks5 is crucial for invadopodia formation. The structural similarities between Tks5 and p47phox, which is part of the NADPH oxidase (Nox) system, led Dr. Courtneidge to consider the role reactive oxygen plays in invadopodia formation.. Using invadopodia-rich mouse fibrosarcoma cells, the Courtneidge laboratory tested a number of antioxidants and found both a marked reduction in invadopodia formation and invasive behavior. In addition, the team inhibited expression of Nox family enzymes with siRNA and had similar results, demonstrating that NADPH oxidases are involved in invadopodia formation. The scientists repeated these experiments with human melanoma, head and neck and breast cancer cell lines and also saw a marked reduction in invadopodia formation.. With the discovery of reactive oxygens role in invadopodia ...
The past decade has seen the definition of key signalling pathways downstream of receptor tyrosine kinases (RTKs) in terms of their components and the protein-protein interactions that facilitate signal transduction. Given the strong evidence that links signalling by certain families of RTKs to the progression of breast cancer, it is not surprising that the expression profile of key downstream signalling intermediates in this disease has also come under scrutiny, particularly because some exhibit transforming potential or amplify mitogenic signalling pathways when they are overexpressed. Reflecting the diverse cellular processes regulated by RTKs, it is now clear that altered expression of such signalling proteins in breast cancer may influence not only cellular proliferation (eg Grb2) but also the invasive properties of the cancer cells (eg EMS1/cortactin).
Recent studies have indicated that detachment of epithelial cells triggers not only pro-apoptotic but also anti-apoptotic signals, and the equilibrium between these signals regulates anoikis (22-24). In suspended carcinoma cells, survival signals typically prevail, and anoikis induction is blocked, ultimately leading to tumor invasion and metastasis. Several anti-anoikis signals in cancer cells have been identified. For example, we and other researchers found that the activation of oncoproteins, including CTTN (14), calreticulin (15), Ras (25, 26), and β-catenin (17), suppressed anoikis of various types of cancer cells. In the present study, we found that detachment of ESCC cells triggered the upregulation of PLK1, a critical anti-apoptotic protein. Overexpression of PLK1 blocked anoikis in detached cells, and inhibition or depletion of PLK1 restored the sensitivity of ESCC cells to anoikis. Furthermore, it was noticed that PLK1 depletion did not affect the expression level of CTTN and ...
LSP1 Full-Length MS Protein Standard (NP_002330), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. This gene encodes an intracellular F-actin binding protein. The protein is expressed in lymphocytes, neutrophils, macrophages, and endothelium and may regulate neutrophil motility, adhesion to fibrinogen matrix proteins, and transendothelial migration. Alternative splicing results in multiple transcript variants encoding different isoforms.
Expression of CTTNBP2 (C7orf8, CORTBP2, KIAA1758, Orf4) in stomach 1 tissue. Antibody staining with HPA044654 and CAB009151 in immunohistochemistry.
Expression of CTTNBP2 (C7orf8, CORTBP2, KIAA1758, Orf4) in kidney tissue. Antibody staining with HPA044654 and CAB009151 in immunohistochemistry.
The pSUPER.retro (Oligoengine) RNA interference system was used to achieve stable expression of siRNAs. Oligonucleotides targeted to calpain 2 or PTP1B mRNA as well as a nonsilencing control were synthesized by Integrated DNA Technologies, annealed, and cloned into the pSUPER.retro.puro vector according to manufacturers instructions. Retroviral transfection was performed as described previously (Franco et al., 2004a). Wild-type MTLn3 cells were infected at 32°C for 6 h and allowed to recover in growth medium for 24 h before selection with 1 μg/ml puromycin for 4-5 d. Target sequences for calpain 2 in MTLn3 cells: control, 5′-TTCTCCGAACGTGTCACGT-3′; Capn2 si-A, 5′-AGGCCTATGCCAAGATCAA-3′; and Capn2 si-B, 5′-GAATGGCGATTTCTGCATC-3′. Target sequences for PTP1B in MTLn3 cells: PTP1B si-A, 5′-GCTGACACTGATCTCTGAA-3′; and PTP1Bsi-B, 5′-CAGGAGGAGCCTTGGTGTC-3′. Target sequences for human calpain 2 have been described previously (Su et al., 2006). Target sequences for cortactin: ...
The dissemination of cancer cells from the primary tumor to a distant site, known as metastasis, is the main cause of mortality in cancer patients. Metastasis is a very complex cellular process that involves many steps, including the breaching of the basement membrane (BM) to allow the movement of cells through tissues. The BM breach occurs via highly regulated and localized remodeling of the extracellular matrix (ECM), which is mediated by formation of structures, known as invadopodia, and targeted secretion of matrix metalloproteinases (MMPs). Recently, invadopodia have emerged as key cellular structures that regulate the metastasis of many cancers. Furthermore, targeting of various cytoskeletal modulators and MMPs has been shown to play a major role in regulating invadopodia function. Here, we highlight recent findings regarding the regulation of protein targeting during invadopodia formation and function.
Our results suggest that the inhibitory effect of adrenomedullin on the expression of HGF and COX-2 is mediated by CGRP receptors. DFT calculations of structures, (13)C NMR chemical shifts, and Raman RBM mode of simple models of small-diameter zigzag (4,0) carboxylated single-walled carbon nanotubes. At the end of the experiment, the corneas were processed for histological study. The patients with HK2 expression showed a worse prognosis compared to the HK2 negative cases, and patients who were negative in Bcl-2 and positive in HK2 represented the lowest survival rate. In this paper we have shown for first time that cationically modified pullulan has antiatherogenic potential and influences on lipid metabolism. Tissue was sampled generic cialis from the cranial part of the distal intermediate ridge of the tibia in the tarso-crural joint. Cortactin, an actin-interacting protein, is implicated in cytoskeletal architecture and often amplified in several types of cancer including gastric ...
View mouse Afap1l2 Chr19:56912361-57008228 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Z disc, actin filament binding, cardiac muscle fiber development, regulation of cell migration, regulation of cytoskeleton organization
Activity-regulatedcytoskeleton-associated protein (Arc) protein is implicated as a master regulator of long-term forms of synaptic plasticity and memory formation, but the mechanisms controlling Arc protein function are little known. LTP consolidation requires a period of sustained Arc synthesis driven by brain-derived neurotrophic factor (BDNF) signaling. Local infusion of the BDNF scavenger, TrkB-Fc, during LTP maintenance resulted in rapid reversion of LTP, inhibition of Arc synthesis and loss of enhanced Arc SUMO1ylation. Furthermore, coimmunoprecipitation analysis showed that SUMO1-ylated Arc forms a complex with the F-actin-binding protein drebrin A, a major regulator of cytoskeletal dynamics in dendritic spines. Although MPSL1 Arc also interacted with dynamin 2, calcium/calmodulindependentprotein kinase II-beta (CaMKII), and postsynaptic density protein-95 (PSD-95), these complexes lacked SUMOylated Arc. The results support a model in which newly synthesized Arc is SUMOylated and targeted ...
Invadosomes are actin-based structures involved in extracellular matrix degradation. Invadosomes is a term that includes podosomes and invadopodia, which decorate normal and tumour cells, respectively. They are mainly organised into dots or rosettes, and podosomes and invadopodia are often compared and contrasted. Various internal or external stimuli have been shown to induce their formation and/or activity. In this Commentary, we address the impact of the microenvironment and the role of matrix receptors on the formation, and dynamic and degradative activities of invadosomes. In particular, we highlight recent findings regarding the role of type I collagen fibrils in inducing the formation of a new linear organisation of invadosomes. We will also discuss invadosome plasticity more generally and emphasise its physio-pathological relevance. ...
human AFAP1L1 gene cDNA, cloning vector & expression plasmid, mutiple tags. Optimized for high expression in mammalian cells. Save up to 60%.
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Navy Veteran Daniel Shockley was diagnosed with AFAP, a rare genetic condition affecting the colon, at age 51. Daniel told us his story in a Q&A.
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Muriel, Olivia; Tomas, Alejandra; Scott, Cameron C.; Gruenberg, Jean (2016-11-01). "Moesin and cortactin control actin- ...
Rac1 induces cortactin to localize to the cell membrane, where it simultaneously binds F-actin and Arp2/3. The result is a ... Another molecule that is often found in polymerizing actin with Arp2/3 is cortactin, which appears to link tyrosine kinase ... "Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex". ...
CHO1 Cortactin CamKinase II Calponin Chondramide Cortexillin CAP Caltropin CH-ILKBP CPb3 Cap100 Calvasculin Ciboulot Coactosin ...
... cortactin MeSH D12.644.360.024.295 - crk-associated substrate protein MeSH D12.644.360.024.297 - grb2 adaptor protein MeSH ...
Bourguignon LY, Zhu H, Shao L, Chen YW (Mar 2001). "CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton ...
Agonist-dependent interaction of the rat somatostatin receptor subtype 2 with cortactin-binding protein 1.". J. Biol. Chem. 274 ...
Bourguignon, L Y; Zhu H, Shao L, Chen Y W (March 2001). "CD44 interaction with c-Src kinase promotes cortactin-mediated ...
cortactin. References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000015285 - Ensembl, May 2017 ...
The functions of caveolins are still under intensive investigation. They are best known for their role in the formation of 50-nanometer-size invaginations of the plasma membrane, called caveolae. Oligomers of caveolin form the coat of these domains. Cells that lack caveolins also lack caveolae. Many functions are ascribed to these domains, ranging from endocytosis and transcytosis to signal transduction. Caveolin-1 has also been shown to play a role in the integrin signaling. The tyrosine phosphorylated form of caveolin-1 colocalizes with focal adhesions, suggesting a role for caveolin-1 in migration. Indeed, downregulation of caveolin-1 leads to less efficient migration in vitro. Genetically engineered mice that lack caveolin-1 and caveolin-2 are viable and fertile, showing that neither the caveolins nor the caveolae are essential in embryonic development or reproduction of these animals. However, knock-out animals do develop abnormal, hypertrophic lungs, and cardiac myopathy, leading to a ...
This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the mouse ortholog. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer.[6] ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Shop a large selection of products and learn more about Cortactin Rabbit anti-Mouse, Rat, Polyclonal, Novus Biologicals:: 100 ... Cortactin Polyclonal antibody specifically detects Cortactin in Mouse, Rat samples. It is validated for Western Blot, KnockDown ... 1110020L01Rik, Amplaxin, cortactin, ems1 sequence (mammary tumor and squamous cell carcinoma-associated (p80/85 srcsubstrate), ... Recombinant fusion protein containing a sequence corresponding to amino acids 1-200 of human Cortactin (NP_612632.1).. ...
... and have named the original cortactin as cortactin-A and the newly isolated forms as cortactin-B and -C. Cortactin-A, -B and -C ... Cortactin is a major phosphotyrosyl protein in pp60v-src-transformed chicken embryo cells. Cortactin binds to actin filament (F ... A deletion mutant analysis of cortactin-A and CBP90 revealed that the SH3 domain of cortactin-A was able to bind to the proline ... Isolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90.. Ohoka Y1, Takai Y. ...
Knockout Tested Rabbit recombinant monoclonal Cortactin antibody [EP1922Y]. Validated in WB, IP, IHC, Flow Cyt, ICC/IF and ... Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 488) (ab202648) *Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 647) (ab202650 ... Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 555) (ab215298) *Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 568) (ab215299 ... Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 594) (ab215300) *Anti-Cortactin antibody [EP1922Y] - BSA and Azide free ( ...
... cortactin phosphorylation, cortactin-WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC ... Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of ... PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration.. [Jagadeesh Janjanam, ... MCP1, a G protein-coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time- ...
... or cortactin-specific siRNAs. 48 h later, cell lysates were immunoblotted for cortactin expression (top). Cortactin immunoblots ... human cortactin-6 (5′-ATGCAACTTATTGTATCTGAA-3′), murine cortactin-5 (5′-CAGAGATGTGCTAGTGGCTTA-3′), and murine cortactin-7 (5′- ... Cortactin is an actin-binding protein that promotes actin assembly (Ammer and Weed, 2008). Cortactin is ubiquitously expressed ... Generation of cortactin-deficient mice. (A) Domain organization of the cortactin protein and gene targeting strategy showing ...
Thus, cortactin, unexpectedly, is an important integration node for the dynamic regulation of protein complexes during ... The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. Here, we ... Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of cortactin downstream of RhoA and PKD1 is ... In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of ...
To this end, cells were transfected with cortactinWT, cortactinY421,466,482F and cortactinY421D after cortactin knockdown (Fig ... cortactinS113D and cortactinWT after siRNA-mediated endogenous cortactin knockdown (Fig. 4C). Expression of cortactinS113A on a ... transient expression of cortactinΔNTA, cortactinW22A and cortactinΔSH3 substantially inhibited both, compared with cortactinWT- ... D) A375MM cells were transfected with cortactinWT, nonphosphorylatable cortactinS113A and pseudophosphorylated cortactinS113D. ...
Here, by modulation of cortactin expression in a panel of HNSCC cell lines, we show that cortactin overexpression enhances ... we identified a novel role for cortactin in cancer cells, whereby cortactin overexpression attenuated ligand-induced down- ... Therefore, cortactin may modulate signaling by a broader range of receptors than originally proposed and thereby affect a ... These findings indicate that cortactin may play multiple roles in progression of HNSCC and should be evaluated as a marker of ...
... and these processes require the binding of tyrosine-phosphorylated cortactin, an actin binding protein, with the Rho-family ... The authors found that two tyrosine-phosphorylated residues on cortactin (Y421 and Y466) bind the SH2 domain of Vav2, a guanine ... Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in ... Tyrosine-phosphorylated cortactin recruits Vav2 to invadopodia, which facilitates their maturation and subsequent invadopodia- ...
Anti-Cortactin antibody (Alexa Fluor® 488) [EP1922Y] (ab202648). Anti-Cortactin antibody (Alexa Fluor® 647) [EP1922Y] (ab202650 ... Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 555) (ab215298) *Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 568) (ab215299 ... Anti-Cortactin antibody [EP1922Y] (Alexa Fluor® 594) (ab215300) *Anti-Cortactin antibody [EP1922Y] - BSA and Azide free ( ... ab81208 staining Cortactin in wild-type HAP1 cells (top panel) and Cortactin knockout HAP1 cells (bottom panel). The cells were ...
The incubation of dynamin 2 and cortactin with F-actin induced the formation of long and thick actin bundles, with these ... Actin bundling by dynamin 2 and cortactin is implicated in cell migration by stabilizing filopodia in human non-small cell lung ... Furthermore, dynamin 2 and cortactin mostly colocalized along F-actin bundles in filopodia of serum-stimulated H1299 cells by ... Knockdown of dynamin 2 or cortactin inhibited the formation of filopodia in serum-stimulated H1299 cells, concomitant with a ...
We use cortactin, a Src substrate, and MT1-MMP, an extracellular matrix-degrading, membrane protein, to identify and study the ...
Cortactin, SH3 domain (IPR035716). Short name: Cortactin_SH3 Overlapping homologous superfamilies *SH3-like domain superfamily ... Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich ... Cortactin was originally identified as a substrate of Src kinase [PMID: 2110361]. It is an actin regulatory protein that binds ... Roles of cortactin, an actin polymerization mediator, in cell endocytosis.. Acta Biochim. Biophys. Sin. (Shanghai) 38 95-103 ...
Cortactin lies significantly farther from the PSD than α-actinin. B, Distances of gold particles coding for cortactin from the ... Cortactin in dendrites. We found that cortactin is also concentrated in dendritic shafts, although to a lesser degree than in ... However, cortactin has also been implicated in the morphogenesis of dendritic trees: δ-catenin can bind to cortactin (Weed et ... Spine morphology and cortactin. Recent experiments in cultured neurons (Hering and Sheng, 2003) suggest a role for cortactin in ...
IPR015503, Cortactin. IPR035716, Cortactin_SH3. IPR003134, Hs1_Cortactin. IPR036028, SH3-like_dom_sf. IPR001452, SH3_ ... IPR015503, Cortactin. IPR035716, Cortactin_SH3. IPR003134, Hs1_Cortactin. IPR036028, SH3-like_dom_sf. IPR001452, SH3_ ... CortactinImported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a href="/ ... tr,F6X4S0,F6X4S0_HORSE Cortactin OS=Equus caballus OX=9796 GN=CTTN PE=4 SV=3 ...
Cortactin competes with both full-length CaD and its C-terminal fragment for actin binding. Binding of cortactin partially ... Direct interaction between caldesmon and cortactin Arch Biochem Biophys. 2006 Dec 15;456(2):175-82. doi: 10.1016/j.abb.2006.07. ... Cortactin is another actin-binding protein found mainly in the cell cortex. There have been no reports suggesting that CaD and ... The interaction involves the N-terminal region of cortactin and the C-terminal region of CaD, and appears to be enhanced by ...
While the list of cellular functions influenced by cortactin grows, the ability of cortactin to interact with and … ... cortactin has emerged as a key signaling protein in many cellular processes, including cell adhesion, migration, endocytosis, ... While the list of cellular functions influenced by cortactin grows, the ability of cortactin to interact with and alter the ... Cortactin branches out: roles in regulating protrusive actin dynamics Cell Motil Cytoskeleton. 2008 Sep;65(9):687-707. doi: ...
Knockout Tested Mouse monoclonal Cortactin antibody [4F11]. Validated in WB, IP, ICC, ICC/IF and tested in Mouse, Rat, Chicken ... I can only see a single band at ˜ 100 kD that is not present in the total cortactin gel and cannot possibly be cortactin. I ... It may be possible that the ˜100 kDa band corresponds to the phosphorylated form of cortactin. Since the cortactin antibody ... No band was observed when CTTN (Cortactin) knockout samples were used. Wild-type and CTTN (Cortactin) knockout samples were ...
Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway.. [Marco A O Magalhaes, Daniel R Larson, ... Cortactin phosphorylation is a key step during invadopodia maturation, regulating Nck1 binding and cofilin activity. The ... We provide evidence that cortactin-cofilin binding is regulated by local pH changes at invadopodia that are mediated by the ... Furthermore, cortactin tyrosine phosphorylation mediates the recruitment of NHE1 to the invadopodium compartment, where it ...
To examine the role of cortactin in tumor progression, wild-type cortactin and a tyrosine phosphorylation-deficient cortactin ... In vitro, cortactin binds to and cross-links F-actin into meshwork. The F-actin cross-linking activity of cortactin can be ... Overexpression of GFP-Cortactin Variants Did Not Affect the Growth of Breast Cancer Cells.. To study the effect of cortactin on ... Expression of GFP-cortactin proteins was further quantified by immunoblot analysis. As shown in Fig. 1 ⇓ , both GFP-cortactin ...
However, the function of cortactin in epithelial-mesenchymal transition (EMT) remains elusive. Here we found that during ... Cortactin is an F-actin binding protein, regulating cell movement and adhesive junction assembly. ... Inhibition of the dephosphorylation of cortactin by sodium vanadate blocked TGF-beta1-induced EMT. Knockdown of cortactin by ... Cortactin / physiology*. Epithelial Cells / physiology. Histone Acetyltransferases / physiology. Humans. Kidney / cytology*. ...
Rabbit Polyclonal Cortactin antibody [N1], N-term. Validated in WB, ICC/IF, IHC-P. Tested in Human, Mouse, Rat. Cited in 3 ... Green: Cortactin protein stained by Cortactin antibody [N1], N-term (GTX100253) diluted at 1:500.. Blue: Hoechst 33342 staining ... Cortactin antibody [N1], N-term detects Cortactin protein at cell membrane and cytoplasm by immunofluorescent analysis.. Sample ... There are currently no reviews for Cortactin antibody [N1], N-term (GTX100253). Be the first to share your experience with this ...
miR-326 maturation is crucial for VEGF-C driven cortactin expression and esophageal cancer progression. Chih-Chen Hong, Pai- ... Here we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin ( ... miR-326 maturation is crucial for VEGF-C driven cortactin expression and esophageal cancer progression ... miR-326 maturation is crucial for VEGF-C driven cortactin expression and esophageal cancer progression ...
OMIM: CORTACTIN-BINDING PROTEIN 2; CTTNBP2*Gene Ontology: Cttnbp2 *Mouse Phenome DB: Cttnbp2 *UCSC: Chr.6:18,366,477-18,514,825 ... cortactin binding protein 2. Synonyms: 3010022N24Rik, 4732477G22Rik, 9130022E09Rik, Cortbp2, ORF4. Gene nomenclature, locus ...
In addition, ATAT1 colocalizes with cortactin at the adherent surface of the cells and it is required for 2D migration and ... We previously found that in breast tumor MDA-MB-231 cells an increase of microtubule and cortactin acetylation upon inhibition ... We observed that ATAT1 tubulin acetyltransferase binds and regulates cortactin acetylation levels. ... In addition, ATAT1 colocalizes with cortactin at the adherent surface of the cells and it is required for 2D migration and ...
Cortactin Adopts a Globular Conformation and Bundles Actin into Sheets. Citation. Cowieson, N, King, G, Cookson, D et al 2008 ... Cortactin Adopts a Globular Conformation and Bundles Actin into Sheets, Journal of Biological Chemistry, vol. 283, no. 23, pp ...
... human cortactin) suggest that it may link signaling events to reorganization of the actin cytoskeleton. Interestingly, the EMS1 ... human cortactin) suggest that it may link signaling events to reorganization of the actin cytoskeleton. Interestingly, the EMS1 ... The structural characteristics of EMS1 (human cortactin) suggest that it may link signaling events to reorganization of the ... Signaling pathways and structural domains required for phosphorylation of EMS1/cortactin. Abstract. ...
... pY421-cortactin or pY466-cortactin in invadopodia was quantified, and the pY421-cortactin/cortactin-TagRFP or pY466-cortactin/ ... Cortactin-Nck1 FRET acceptor photobleaching. Cortactin-TagRFP cells lines in which endogenous cortactin was transiently knocked ... Cortactin-Nck1 colocalization analysis. Cortactin-TagRFP cells lines in which endogenous cortactin was transiently knocked down ... Cortactin-Nck1 sensitized emission FRET. MDA-MB-231 cells expressing Nck1 WT-GFP and cortactin WT-TagRFP were subjected to live ...
Cortactin, a Src substrate of 80/85 kDa, is an F-actin binding protein enriched in the cell cortex.J. Cell Biol. 120 1993 1417 ... Down-regulation of F-actin cross-linking activity of cortactin/EMS1 by Src-mediated Tyr phosphorylation.J. Biol. Chem. 272 1997 ... Cortactin/EMS1 is the first identified molecule that is dissociated in a Rac-phosphatidylinositol 4,5-biphosphate (PIP2)- ... HS1 is closely related to an F-actin cross-linking protein called cortactin/EMS1, both structurally and functionally, ...
In this study, we tested the hypotheses that the Src family kinase-cortactin pathway mediates association of ICAM-1 with the ... Our data suggest a model in which tyrosine phosphorylation of cortactin dynamically links ICAM-1 to the actin cytoskeleton, ... Cytoskeletal remodeling after ICAM-1 cross-linking was reduced by knockdown of cortactin by small interfering RNA, by ... We recently reported that Src kinase phosphorylation of endothelial cortactin regulates polymorphonuclear cell (PMN) ...
Cortactin (McNiven et al 2000 J Cell Biol) The chromosome region covering cortactin (EMS1) is amplified in several human ... Overexpression of cortactin increases cell motility and thus may enhance the invasion/metastatic spread of cancers. The link ...
Coincident with Cortactin at some of these sites of dynamic actin are two Cortactin-binding proteins, Cortactin-binding protein ... Naus and Cortactin regulate one anothers dynamics in a reciprocal manner. Our kinetic studies of Naus and Cortactin reveal a ... 2012). Cortactin-binding protein 2 modulates the mobility of cortactin and regulates dendritic spine formation and maintenance ... 1998). Isolation and characterization of cortactin isoforms and a novel cortactin-binding protein, CBP90. Genes Cells 3, 603- ...
  • Recombinant fusion protein containing a sequence corresponding to amino acids 1-200 of human Cortactin (NP_612632.1). (fishersci.com)
  • Synthetic peptide within Human Cortactin aa 1-100 (N terminal). (abcam.com)
  • These results suggest that cortactin interacts with CBP90 and plays a role in regulation of the actin cytoskeleton in brain. (nih.gov)
  • The CTTN gene (formerly designated EMS1), encodes cortactin, a key regulator of dynamic actin networks. (garvan.org.au)
  • Cortactin binds to actin filament (F-actin) through a unique region which consists of six tandem 37 amino acid repeats, named cortactin repeats. (nih.gov)
  • In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1;also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution. (uni-muenchen.de)
  • Tyrosine-phosphorylated cortactin recruits Vav2 to invadopodia, which facilitates their maturation and subsequent invadopodia-mediated matrix degradation and cancer cell invasion. (cytoskeleton.com)
  • Invadopodial function depends upon re-arrangement of the actin cytoskeleton, all of which requires phospho-cortactin-mediated recruitment of Vav2 to the invadopodia. (cytoskeleton.com)
  • Previously, we identified a novel role for cortactin in cancer cells, whereby cortactin overexpression attenuated ligand-induced down-regulation of the epidermal growth factor (EGF) receptor (EGFR), leading to sustained signaling. (garvan.org.au)
  • Here, by modulation of cortactin expression in a panel of HNSCC cell lines, we show that cortactin overexpression enhances serum- and EGF-stimulated proliferation under both anchorage-dependent and anchorage-independent conditions and also increases resistance to anoikis (detachment-induced apoptosis). (garvan.org.au)
  • Finally, we have determined that cortactin overexpression, either alone or in combination with cyclin D1 up-regulation, promotes resistance to the EGFR kinase inhibitor gefitinib. (garvan.org.au)
  • Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. (sigmaaldrich.com)
  • Cortactin Polyclonal antibody specifically detects Cortactin in Mouse, Rat samples. (fishersci.com)
  • PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration. (sigmaaldrich.com)
  • Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required for cell migration. (sigmaaldrich.com)
  • In addition, the MCP1-induced cortactin phosphorylation is dependent on PLCβ3-mediated PKCδ activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, affecting G-actin polymerization, F-actin stress fiber formation, and HASMC migration. (sigmaaldrich.com)
  • Upstream, MCP1 activates CCR2 and Gαq/11 in a time-dependent manner, and down-regulation of their levels attenuates MCP1-induced PLCβ3 and PKCδ activation, cortactin phosphorylation, cortactin-WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC migration. (sigmaaldrich.com)
  • Two new S298-phosphorylation-dependent interactions were also identified, namely, that phosphorylation of cortactin decreases its interaction with beta-catenin and the actin-binding protein vinculin. (uni-muenchen.de)
  • MCP1, a G protein-coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. (sigmaaldrich.com)
  • The authors found that two tyrosine-phosphorylated residues on cortactin (Y421 and Y466) bind the SH2 domain of Vav2, a guanine nucleotide exchange factor (GEF) for Rho-family GTPases such as Rac. (cytoskeleton.com)
  • In this study we have isolated two new isoforms of cortactin from the rat brain using a polymerase chain reaction (PCR) method, and have named the original cortactin as cortactin-A and the newly isolated forms as cortactin-B and -C. Cortactin-A, -B and -C had six, five, and four cortactin repeats, respectively. (nih.gov)
  • The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. (uni-muenchen.de)
  • These findings indicate that cortactin may play multiple roles in progression of HNSCC and should be evaluated as a marker of prognosis, disease progression, and therapeutic responsiveness, particularly to EGFR-directed agents. (garvan.org.au)
  • Cortactin is a major phosphotyrosyl protein in pp60v-src-transformed chicken embryo cells. (nih.gov)
  • 2017. Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells. (cytoskeleton.com)
  • Here, we were interested to study the broader functional interactions of cortactin in adhesion complexes. (uni-muenchen.de)
  • Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of cortactin downstream of RhoA and PKD1 is vitally dependent on vinculin-mediated protein interactions. (uni-muenchen.de)
  • Next, using a blot overlay assay with glutathione S-transferase (GST)-cortactin-A, we identified a cortactin-A-binding protein with an Mr of approximately 90 kDa in rat brain and named it CBP90 (cortactin-binding protein with an Mr of approximately 90 KDa). (nih.gov)
  • A deletion mutant analysis of cortactin-A and CBP90 revealed that the SH3 domain of cortactin-A was able to bind to the proline-rich region of CBP90. (nih.gov)
  • Rabbit anti-human cortactin antibody recognizes Src substrate cortactin, also known as amplaxin or oncogene EMS1. (bio-rad-antibodies.com)
  • Rabbit anti Human cortactin antibody recognizes the Src substrate cortactin, also known as amplaxin, ems1 sequence (mammary tumor and squamous cell carcinoma-associated (p80/85 src substrate) or oncogene EMS1. (bio-rad-antibodies.com)
  • Dsg3 co-localized along cell contacts and interacted with the Src substrate cortactin. (helmholtz-hzi.de)
  • Here we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin (CTTN), a regulator of the cortical actin cytoskeleton. (aacrjournals.org)
  • Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, thus controls dendritic spinogenesis and dendritic spine maintenance. (nih.gov)
  • The CTTN gene consists of 18 exons, which code for the protein cortactin. (biotechniques.org)
  • Cortactin has a multidomain structure consisting of binding regions for the Arp2/3 (actin-related protein 2/3) complex and F-actin. (rupress.org)
  • Here, a new invadopodia synchronization protocol is used to show that the cortactin N-terminal acidic and SH3 domains, involved in Arp2/3 complex and N-WASP binding and activation, respectively, are both required for invadopodia biogenesis. (biologists.org)
  • We found that Naus co-localizes with F-actin and Cortactin in the lamellipodia of Drosophila S2R+ and D25c2 cells and this localization is lost following Cortactin or Arp2/3 depletion or by mutations that disrupt a conserved proline patch found in its mammalian homologs. (biologists.org)
  • Cortactin is a Src substrate that interacts with F-actin and can stimulate actin polymerization by direct interaction with the Arp2/3 complex. (elsevier.com)
  • 2011). Cortactin regulates branched F-actin assembly by interacting with the Arp2/3 complex at its N-terminus, binding to F-actin at its cortactin repeats, and binding N-WASP at its C-terminal SH3 domain (Kirkbride et al. (biotechniques.org)
  • Although cortactin is a weak activator of the Arp2/3 complex when compared to class I NPFs (e.g. (mechanobio.info)
  • A. Cortactin stabilizes Arp2/3-mediated actin nucleation. (mechanobio.info)
  • Another molecule that is often found in polymerizing actin with Arp2/3 is cortactin, which appears to link tyrosine kinase signalling to cytoskeletal reorganization in the lamellipodium and its associated structures. (wikipedia.org)
  • Rac1 induces cortactin to localize to the cell membrane, where it simultaneously binds F-actin and Arp2/3. (wikipedia.org)
  • While cortactin-mediated activation of Arp2/3 complex and invadopodia regulation has been well established, signaling pathways responsible for governing cortactin binding to Arp2/3 are unknown. (wvu.edu)
  • In this dissertation we identify casein kinase (CK) 2α phosphorylation of cortactin as a negative regulator of Arp2/3 binding. (wvu.edu)
  • CK2α directly phosphorylates cortactin at a conserved threonine (T24) adjacent to the canonical Arp2/3 binding motif. (wvu.edu)
  • Phosphorylation of cortactin T24 by CK2α impairs the ability of cortactin to bind Arp2/3 and activate actin nucleation. (wvu.edu)
  • Cortactin variants containing the NTA region are inefficient at promoting Arp2/3 actin nucleation activity. (sdbonline.org)
  • These data provide strong evidence that cortactin is specifically localized to sites of dynamic cortical actin assembly via simultaneous interaction with F-actin and the Arp2/3 complex. (sdbonline.org)
  • Cortactin binds to Arp2/3 complex, the essential molecular machine for nucleating actin filament assembly. (sdbonline.org)
  • Cortactin is shown to activate Arp2/3 complex, based on direct visualization of filament networks and pyrene actin assays. (sdbonline.org)
  • Cortactin regulates podosome formation: roles of the protein interaction domains. (ebi.ac.uk)
  • Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway. (sigmaaldrich.com)
  • We show that this mechanism involving cortactin phosphorylation, local pH increase, and cofilin activation regulates the dynamic cycles of invadopodium protrusion and retraction and is essential for cell invasion in 3D. (sigmaaldrich.com)
  • We observed that ATAT1 tubulin acetyltransferase binds and regulates cortactin acetylation levels. (archives-ouvertes.fr)
  • We recently reported that Src kinase phosphorylation of endothelial cortactin regulates polymorphonuclear cell (PMN) transmigration. (butler.edu)
  • Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. (ebi.ac.uk)
  • Cortactin: Coordinating adhesion and the actin cytoskeleton at cellular protrusions. (ebi.ac.uk)
  • Cosen-Binker LI, Kapus A. Cortactin: the gray eminence of the cytoskeleton. (ebi.ac.uk)
  • We performed immunocytochemical experiments to find out whether cortactin is present in spiny neurons of the rat brain, and, if so, whether it concentrates in a location suited to transduce interactions between the synapse and the actin cytoskeleton. (jneurosci.org)
  • These results suggest that cortactin interacts with CBP90 and plays a role in regulation of the actin cytoskeleton in brain. (nih.gov)
  • Thus, cortactin appears to act as a signaling molecule in the regulation of the dynamics of actin cytoskeleton in a tyrosine phosphorylation-dependent manner. (aacrjournals.org)
  • Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. (sigmaaldrich.com)
  • In this study, we tested the hypotheses that the Src family kinase-cortactin pathway mediates association of ICAM-1 with the actin cytoskeleton and that this association is required for ICAM-1 clustering and leukocyte transmigration. (butler.edu)
  • Our data suggest a model in which tyrosine phosphorylation of cortactin dynamically links ICAM-1 to the actin cytoskeleton, enabling ICAM-1 to form clusters and facilitate leukocyte transmigration. (butler.edu)
  • Invadopodial function depends upon re-arrangement of the actin cytoskeleton, all of which requires phospho-cortactin-mediated recruitment of Vav2 to the invadopodia. (cytoskeleton.com)
  • Perturbation of the cytoskeleton indicated that cortactin distribution largely depends on actin filaments. (elsevier.com)
  • The function of cortactin at PSDs is not yet clear but it is speculated to facilitate changes in the actin cytoskeleton in response to synaptic activity. (mechanobio.info)
  • The tyrosine phosphorylation of cortactin and its ability to associate with the actin cytoskeleton were required in tandem for the regulation of cell motility. (biomedcentral.com)
  • We show that invasion of HeLa cells by S.flexneri induces tyrosine phosphorylation of cortactin, a host cell protein previously identified as a cytoskeleton-associated protein tyrosine kinase (PTK) substrate for the proto-oncoprotein pp60c-src. (pasteur.fr)
  • The properties of cortactin indicate that it may be important for microfilament-membrane interactions as well as transducing signals from the cell surface to the cytoskeleton. (sdbonline.org)
  • This study presents the first evidence that pp60(c-src) can directly regulate the activity of its substrate toward the cytoskeleton and implies a role for cortactin as an F-actin modulator in tyrosine kinase-regulated cytoskeleton reorganization (Huang, 1997). (sdbonline.org)
  • NHE1-related acidic pH enzyme activation, ankyrin/cortactin-actin binding and PI3 kinase/AKT-mediated biological activities) required for ECM degradation, cytoskeleton function and metastatic tumor cell properties. (labome.org)
  • The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. (uni-muenchen.de)
  • The multidomain protein cortactin, which is involved in the regulation of actin polymerisation, is one such component, but how cortactin is modulated to control the formation of invadopodia has not been elucidated. (biologists.org)
  • The actin-binding protein cortactin facilitates branched actin network formation through activation of the actin-related protein (Arp) 2/3 complex. (wvu.edu)
  • and Wilder, Jannell, "Phosphorylation of the Actin Binding Protein Cortactin by Aurora Kinase" (2011). (linfield.edu)
  • Our lab previously uncovered a role for the actin-associated protein cortactin as an enhancer of membrane protrusions in cultured neurons and for calpain as an inhibitor of this process in consolidated regions. (ubc.ca)
  • To explore the role of cortical actin-binding protein (cortactin) in shear stress-induced mucin (MUC) 5AC secretion in human airway epithelial cells and the effect of phosphorylation of cortactin at different sites. (bvsalud.org)
  • The protein cortactin gathers on branched actin networks, enhancing formation of new branches and stabilizing nascent ones. (rupress.org)
  • Inhibition of host cell c-Src significantly blocked C. parvum-induced accumulation and tyrosine phosphorylation of cortactin and actin polymerization at the attachment sites, thereby inhibiting C. parvum invasion of biliary epithelial cells. (elsevier.com)
  • Conclusions: C. parvum invasion of biliary epithelial cells requires host cell tyrosine phosphorylation of cortactin by a c-Src-mediated signaling pathway to induce actin polymerization at the attachment site, a process associated with microbial secretion but independent of host cell endocytosis. (elsevier.com)
  • HBE16 airway epithelial cells were cultured, and then transfected with mutation carrier, such as pEGFP-N1-cortactin (Cort), pEGFP-N1-Cort-Y421A, pEGFP-N1-Cort-Y470A and pEGFP-N1-Cort-Y486A. (bvsalud.org)
  • Cortactin is involved in shear stress-mediated MUC5AC secretion in human airway epithelial cells, and the phosphorylated site of Tyr421 and Tyr470 may play an important role in it. (bvsalud.org)
  • Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain [ PMID: 15670811 ]. (ebi.ac.uk)
  • Cortactin is composed of an N-terminal acidic domain and a six-and-a-half tandem repeats domain, which directly binds to F-actin. (spandidos-publications.com)
  • Two distinct sequence motifs of cortactin contribute to its interaction with the cortical actin network: the fourth of six tandem repeats and the amino-terminal acidic region (NTA). (sdbonline.org)
  • Cortactin, unlike type I NPFs, can be found integrated within the lamellipodia. (biologists.org)
  • Immunostaining of growth cones revealed a strong colocalization of cortactin with F-actin in filopodial bundles and at the leading edge of lamellipodia. (elsevier.com)
  • Hyperoxia also caused a thickening of the subcortical dense peripheral F-actin band and increased the localization of cortactin in the cortical regions and lamellipodia at cell-cell borders that protruded under neighboring cells. (elsevier.com)
  • Ventral lamellipodia were enriched in the Rac1 effectors cortactin, IQGAP, and p47Phox and exhibited localized production of hydrogen peroxide. (rupress.org)
  • Cortactin, present in several different cell types, is enriched in cortical structures such as membrane ruffles and lamellipodia. (sdbonline.org)
  • Cortactin is an actin-binding protein that is enriched within the lamellipodia of motile cells and in neuronal growth cones. (sdbonline.org)
  • Cortactin is localized with the actin-related protein (Arp) 2/3 complex at sites of actin polymerization within the lamellipodia. (sdbonline.org)
  • 2015. Src and cortactin promote lamellipodia protrusion and filopodia formation and stability in growth cones. (purdue.edu)
  • Direct binding of EC MLCK to the cortactin Src homology 3 domain appears essential to S1P barrier regulation, since cortactin blocking peptide inhibits both S1P-induced MLC phosphorylation and peak S1P-induced TER values. (elsevier.com)
  • Results: Immunofluorescence microscopy revealed that protein kinase C (PKC) α colocalises with cortactin at growth cone filopodia in SH-SY5Y neuroblastoma cells. (elsevier.com)
  • In rat cortical neurons and human neuroblastoma cell line, SH-SY5Y, both dynamin 1 and cortactin localized on actin filaments and the bundles at growth cone filopodia as revealed by immunoelectron microscopy. (elsevier.com)
  • Cortactin knockdown also reduced growth cone filopodia. (elsevier.com)
  • Together, our results strongly suggest that dynamin 1 and cortactin ring complex mechanically stabilizes F-actin bundles in growth cone filopodia. (elsevier.com)
  • Knockdown of dynamin 2 or cortactin inhibited the formation of filopodia in serum-stimulated H1299 cells, concomitant with a loss of F-actin bundles. (spandidos-publications.com)
  • These results indicate that dynamin 2 and cortactin participate in cell migration by stabilizing F-actin bundles in filopodia. (spandidos-publications.com)
  • Here, we report a role for cortactin and the tyrosine phosphorylation of cortactin in hyperoxia-induced NADPH oxidase activation and ROS production in human pulmonary artery ECs (HPAECs). (elsevier.com)
  • The results indicate that the level of cortactin transcript appears to be higher in β5 integrin knockout eyecups in comparison to wild type eyecups (Figure 1). (biotechniques.org)
  • In addition, Western blot and immunofluorescence test indicated CX 3 CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. (omgcb.com)
  • An increase in cortactin expression in β5 integrin knockout eyecups was not observed in the region amplified using primer pairs for exons 2-6. (biotechniques.org)
  • This analysis utilized eyecups and neural retinas from wild-type, β5 integrin knockout mice as well as JNK2 knockout mice, which were originally used to test primer pairs, but were employed here as controls to determine whether the increase in cortactin expression observed in β5 integrin knockout eyecups was specific to that knockout. (biotechniques.org)
  • S1P also induces a rapid increase in cortactin tyrosine phosphorylation (within 30 s) critical to subsequent barrier enhancement, since EC transfected with a tyrosine-deficient mutant cortactin exhibit a blunted TER response. (elsevier.com)
  • Similarly, AK23 impaired reconstitution of cell adhesion was Src-dependent only in the presence of cortactin. (helmholtz-hzi.de)
  • This time-lapse series shows that actin filaments "de-branch" in the presence of cortactin and PI(3,5)P 2 . (rupress.org)
  • Electron microscopic analysis after negative staining further revealed that actin filaments in the presence of cortactin are cross-linked into bundles of various degrees of thickness. (sdbonline.org)
  • Although the biochemical and cellular function of cortactin and its relationship to poor prognosis in a subset of cancers suggest that cortactin may play a role in tumor metastasis, direct evidence is lacking. (aacrjournals.org)
  • However, the function of cortactin in epithelial-mesenchymal transition (EMT) remains elusive. (biomedsearch.com)
  • We have isolated complete loss-of-function mutants of the single Drosophila cortactin gene. (elsevier.com)
  • Somogyi, K & Rørth, P 2004, ' Cortactin modulates cell migration and ring canal morphogenesis during Drosophila oogenesis ', Mechanisms of Development , vol. 121, no. 1, pp. 57-64. (elsevier.com)
  • Cortactin enhances elongation of axons in Drosophila. (ubc.ca)
  • Cortactin enhances elongation of axons in Drosophila melanogaster and is inhibited by calpain in vivo by Victoria Roslynne Mains B.Sc. (ubc.ca)
  • Genomic organization, transcription start sites, and chromosomal location of the Drosophila cortactin gene. (semanticscholar.org)
  • Inhibition of the dephosphorylation of cortactin by sodium vanadate blocked TGF-beta1-induced EMT. (biomedsearch.com)
  • We previously found that in breast tumor MDA-MB-231 cells an increase of microtubule and cortactin acetylation upon inhibition of HDAC6 correlates with a decrease of matrix degradation and invasion in three-dimensional collagen I gel. (archives-ouvertes.fr)
  • In keratinocytes isolated from cortactin-deficient mice, cell adhesion was impaired and Src-mediated inhibition of AK23-induced loss of cell cohesion for 24 h was significantly reduced compared to wild-type (wt) cells. (helmholtz-hzi.de)
  • Likewise, Src inhibition significantly reduced AK23-induced skin blistering in wt but not cortactin-deficient mice. (helmholtz-hzi.de)
  • Cortactin phosphorylation as a switch for actin cytoskeletal network and cell dynamics control. (ebi.ac.uk)
  • This review examines how regulation of cortactin through post-translational modifications and interactions with multiple binding partners elicits changes in cortical actin cytoskeletal organization, impacting the regulation and formation of actin-rich motility structures. (nih.gov)
  • Cortactin was originally identified as a substrate of Src kinase [ PMID: 2110361 ]. (ebi.ac.uk)
  • In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1;also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution. (uni-muenchen.de)
  • The EGF receptor-Src-Arg kinase signaling cascade results in phosphorylation of cortactin. (cytoskeleton.com)
  • Therefore, we wanted to test whether the Src kinase substrate and actin regulator cortactin could be a molecular link between Src activity and actin assembly during apCAM-mediated growth cone guidance. (elsevier.com)
  • It was hypothesized that Aurora kinase phosphorylates cortactin on serine 348. (linfield.edu)
  • Cortactin, an F-actin associated protein and a substrate of Src kinase, was found to interact with FAK through its SH3 domain and the C-terminal proline-rich regions of FAK. (biomedcentral.com)
  • RhoGEFs/RacGEF (Tiam1) and c-Src kinase] plays an important role in HA-mediated oncogenic signaling such as the RhoA-activated ROK pathway, Tiam1-regulated Rac1-PKNgamma kinase pathway and c-Src-induced cortactin and Gab-1/PI3 kinase-AKT pathways. (labome.org)
  • Cortactin: coupling membrane dynamics to cortical actin assembly. (ebi.ac.uk)
  • Cortactin is an actin-binding protein that promotes actin assembly ( Ammer and Weed, 2008 ). (rupress.org)
  • Altogether, these data suggest that cortactin is a mediator of IgCAM-triggered actin assembly involved in growth cone motility and guidance. (elsevier.com)
  • 2011). The aim of this study was to characterize cortactin expression in RPE cells since this protein is important for F-actin assembly, as well as in the neural retina to determine if cortactin s expression is unique to the RPE. (biotechniques.org)
  • Cortactin is a c-src substrate associated with sites of dynamic actin assembly at the leading edge of migrating cells. (sdbonline.org)
  • A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. (rupress.org)
  • These data demonstrate a novel function for cortactin and actin in hyperoxia-induced activation of NADPH oxidase and ROS generation in human lung endothelial cells. (elsevier.com)
  • A depolymerization assay revealed that dynamin 1 and cortactin increased the stability of actin bundles, most prominently in the presence of GTP. (elsevier.com)
  • A depolymerization assay revealed that dynamin 2 and cortactin increased the stability of F-actin bundles. (spandidos-publications.com)
  • Mutants are viable and fertile, showing that cortactin is not an essential gene. (elsevier.com)
  • Cortactin is a minor contributor in this regulation, consistent with the cortactin gene not being essential for development. (elsevier.com)
  • The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to amplification of the encoding gene (is most frequently associated with poor clinical outcomes such as decreased patient survival and increased metastasis (34, 43). (biodiversityhotspot.org)
  • Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of cortactin downstream of RhoA and PKD1 is vitally dependent on vinculin-mediated protein interactions. (uni-muenchen.de)
  • Thus, cortactin, unexpectedly, is an important integration node for the dynamic regulation of protein complexes during breakdown and formation of adherens junctions. (uni-muenchen.de)
  • Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. (omgcb.com)
  • Thus, the GTPase-dependent mechanochemical enzyme property of dynamin is commonly used both in endocytosis and regulation of F-actin bundles by a dynamin 1 cortactin complex. (elsevier.com)
  • Antisense down-regulation of cortactin protein expression significantly inhibits S1P-induced barrier enhancement in cultured human pulmonary artery EC as measured by transendothelial electrical resistance (TER). (elsevier.com)
  • Similarly, down-regulation of Src with Src small interfering RNA attenuated the hyperoxia-mediated phosphorylation of cortactin tyrosines and blocked the association of cortactin with actin and p47 phox . (elsevier.com)
  • Here we found that during transforming growth factor-beta1 (TGF-beta1)- induced EMT in AML-12 murine hepatocytes, cortactin underwent tyrosine dephosphorylation. (biomedsearch.com)
  • Therefore, it appears that in vivo, cortactin acts as an enhancer of membrane protrusions and elongation and is actively inhibited by calpain. (ubc.ca)
  • In particular, cortactin is highly enriched in membrane ruffles of the entry structure, which engulf entering bacteria, and also in the periphery of the phagosome early after bacterial internalization. (pasteur.fr)
  • The name cortactin is suggested, reflecting the cortical subcellular localization and its actin-binding activity (Wu, 1993). (sdbonline.org)
  • Using immunocytochemistry, we demonstrate here that cortactin (a protein implicated in actin filament nucleation, branching, and stabilization) is concentrated in hippocampal spines, where it colocalizes with F-actin. (jneurosci.org)
  • In addition, ATAT1 colocalizes with cortactin at the adherent surface of the cells and it is required for 2D migration and invasive migration of MDA-MB-231 cells in collagen matrix. (archives-ouvertes.fr)
  • Our results suggest that cortactin acts as a bridging molecule between actin filaments and focal adhesions. (biomedcentral.com)
  • Taken together, our findings indicate that Sac-1004 blocks vascular leakage by enhancing endothelial integrity via the cAMP/Rac/cortactin pathway and imply the potential usefulness of Sac-1004 in the development of therapeutic means for vascular leakage-related diseases. (elsevier.com)
  • In addition, cortactin has been reported to interact with FAK, a key component of the RPE phagocytic pathway. (biotechniques.org)
  • Cortactin: a multifunctional regulator of cellular invasiveness. (ebi.ac.uk)
  • The optimal F-actin cross-linking activity of cortactin requires a physiological pH in a range of 7.3-7.5. (sdbonline.org)
  • In addition, pp60(c-src) moderately inhibits the F-actin binding activity of cortactin. (sdbonline.org)