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the cell coat- formed from carbohydrate projections from the plasma membrane & mediates cell to cell and cell to substratum interactions |
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7 The extracellular matrix (ECM) |
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an organized network beyond the plasma membrane - plays role in stermining shape and activities of the cell |
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ECM... a cont. sheet that underlies epithelial tissue and surrounds blood vessels. - maintian cell attchm. - substratum for cell migration - barrier to macromolecules |
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Fibrous gycoproteins found only in the ECM. Most abundant protein in the body provide high tensile strength types of collagen speciffic to parts on the body ALL COLLAGENS ARE A TRIMER OF POLYPEPTIDE CHAINS WOUND AROUND EACH OTHER PROVIDE INSOLUABLE FRAMEWORK THAT DETERMINES MECHANICAL PROPERTIES OF THE MATRIX disease: epidermolysis bullosa |
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protein polysaccharide complex, with the core protein attached to glycosaminoglycans (GAGs) - have repeating disaccharide structure -Neg charged gags attract cation which attracts water forming gel |
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a linear array of distinct polypeptides giving it a modular structure -each polypeptide is about 30Fn modules Fn modules are found in other proteins too -FB HAS BINDING SITES FOR OTHER COMPONENTS OF THE ECM -FB IS ONE COMPONENT THAT GUIDES MIGRATING CELLS DURING EMBRYOGENESIS |
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ECM Extracellular glycoproteins consisting of three polypeptide cahins inked by disulfide bonds -HELP CELL MIGRATION DURING DEVELOPMENT -COMPONENTS OF BASEMENT MEMBRANES |
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are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains. |
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are long carbohydrate molecules of monosaccharide units joined together by glycosidic bonds(binds carbohydrtes to another molecule). |
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family of membrane proteins composed of heterodimers with alpha beta subunits -major role in integrating extracellular and intracellular environments/signals. Role in ADHESION TO CELLS TO THEIR SUBSTRATUM OR OTHER CELLS -linkage between integrins and their ligand mediates adhesion between cells and their enviroment -binding of proteins to integrins is facilitated by tripeptde rgd -integrins cytoplasmic domans contain binding sites for cytoplasmic proteins -make connection between ECM and the cytoskeleton |
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scattered, discrete sites for CELL ADHESION TO THEIR SUBSTRATUM IN VITRO -MAY ACT AS A SENSORY STRUCTURE -ARE ALSO IMPLICATED IN CELL LOCOMOTION *key proteins Actin, integrin |
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cell to surface BASAL ATTACHMENTS OF EPITHELIAL CELLS TO THE BASEMENT MEMBRANE IN VIVO -contain a dense plaque with filaments consisting of keratin -KERATIN FILAMENTS ARE LINKED TO THE ECM BY MEMBRANE-SPANNING INTEGRINS *key proteins Keratin and integrin |
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disk shaped in cell to cell interaction -**contain cadherins that link the two cells across a narrow gap -** Cadherins of demosomes have different domain structures: desogleins and desmocollins *keyproteins desoglein and desmocollin (cadherins) |
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7 Focal Adhesions vs. Hemidemosomes |
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FA: outside of the cell in substrate in vitro Inetgrins connect inner to outer cell surface Actin filaments represent internal structures
HemiD: Outside of cell in substrate in vivo Integrins connect inner to outter cell surface Keratin filaments represent internal structures |
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FAMILY OF INTEGRAL MEMBRANEGLYCOPROTEINS THAT BIND TO SUGARS ON THE SURFACE OF THE CELLS -contain a small cytoplasmic domain, a single membrane-spanning domain, and a large extracellular segment Three types: E-endothelial cells P-on platlets and endothelial cells L-on leukocytes |
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7 immunoglobin superfamily (IgSF) |
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most proteins are involved in immune functions. -most igSF molecules mediate interaction of lymphocytes with cells required for immune response -contain fibronectin like domains (FnIII) |
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glycoproteins tbat mediate ca2+ dependent cell-cell adhesion -transmit signals from ECM to the cytoplasm -mediate many of the changes in adhesive contacts during embryonic deleopment through the epithelial-mesenchymal transition (EMT) |
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Migration from one location to another is associated with the loss if cadherin expression, allowing cadherin decficent cells to eliminate their connections with adjacent cells. and become neural tubes |
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- recruitment of leukocytes to site of injury - NEUTROPHILS ATTAH P- and E-Selectins -Neutrophils start to "roll" along wall of vessels |
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7 The role of cell adhesion in inflammation |
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- as neutrophils interact with inflamed venule endotheliium, platelet activating factor (PAF) is displayed -PAF sends a signal to invrease the binding activity of some integrins -Activated integrins casue neutrophils to stop rolling and adhere firmly the wall of vessel |
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The spread of a tumor to other parts of the body |
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7 Mestastic cell properties |
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-are less adhesive -able to penetrate several barriers -able to invade normal tissues |
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7 The role of cell adhesion in metastasis |
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DURING GROWTH AND DEVELOPMENT OF A TUMOR THERE IS LODD OF E-CADHERIN LEADING TO LESS ADHESION -CHANGES IN NUMBERS AND TYPES OF CELL-ADHESION MOLECULES PROMOTE METATASIS |
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**form belts near apical surface called Junctional Complex **cells of an adherens junction held together by calcium-dependent linkages (eg cadherins) *Key proteins : actin, cadherins |
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7 Transmembrane signaling |
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the transer of information across the plasma membrane -** Integrins and cadherins can transmit signals from the extracellular environment to the cytoplasm |
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*specialized contacts between epithelial cells -*located at the very apical end of the junctional complex between adjacent cells -*serve as a barrier to the free diffusion of water and solutes from the extracellular compartment -some are permeable to specffic ions or solutes -form the blood-brain barrier **keyproteins:occudin and claudin |
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form the major structural component of TJs and in the differnce in selective permaiblity |
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**sites between animal cells for intercellular communication - composed entirely of the membrane protein connexin which are organized into a connexon -gj intercellular communincation allows the passage of low-weight molecules -**allow integration of activites of cells into a finctional unit -**compatibility differences between connexins either promote or prevent communication between different cells *key protein: connexin |
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provide plants protection against mechanical abrasion, pathogens, and osmotic stress -the fibrous componet is cellulose -cellulose is organized into microfibrils, (provide cell wall rigidity) -matrix contans HEMICEEULOSES, PECTINS, and PROTEINS -arrise as a ceel plate that forms between plasma membrane and daughter cells -the walls of growing cells are PRIMARY WALLS and allow fexibility that the SECONDARY WALLS in mature cells lack |
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**cytoplasmic channels passing through cell walls of adjacent plant cells -lined by plasma membrane -contain a central structure (desmotuble) -serve as sites of cell-cell communincation |
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15 Extra cellular messenger molecules |
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*transmit messages between cells |
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the cell receptor is on its surface that respond to the messenger |
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messenger molecules travel short distances through extracellular space |
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messenger molecules reach their target cell through the blood stream |
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*Recieve the message -some receptors generate an intracellular second messenger through an enzyme called an EFFECTOR. -other surface receptors recruit proteins to their intracellular domains |
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15 Signaling Pathways in signal transduction |
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consits of a series of proteins - each protein in a pathway alters the conformation of the next protein - protein conformation is usually altered by phosphorylation ( adding a phosphate group to another molecule) -target proteins ultimately receive a message to alter cell activity |
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15 extracellular messengers include... |
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Definition
-small molecules like amino acids and their derivatives -gases such as NO and CO -Eicosanoids,(lipids derived form fatty acids) -peptides and proteins |
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- steroid hormone receptors (NR) -**G-protein coupled recpetors (GPCRs) -** Receptor protein-tyroine kinases RTKs -ligand gated channels -B and T receptors |
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g prtoein coupled receptors are numerous and have seven trans-membrane domain and interact with G proteins |
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15 Signal Transduction by G protein-coupled receptors |
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-Ligand binding on the extracellular domain changes the intracellular domain -affinity for g proteins increases, and the receptor binds G protein intracellularly -GDP is exchanged for GTP on the G protein, activating the G protein -one ligand-bound receptor can activate many g proteins |
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15 Termination of response in G protein couples receptors |
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Definition
-Densensitization- by blocking active receptors turning on additonal G proteins -G protein couldped receeptor kinase GRK -activates a GPCR via phosphorylation -proteins called arrestins compete with G proteins to bind GPCRs -Termination of the response is accelerated by regulators of G protein signaling RGS |
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target GPCRs and Gproteins |
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is a 2nd messenger which amplify the response of the ligand |
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activates protein kinase C which phosphorylates serine and threnine residues on target proteins |
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15 phosphorylated phosphoinositides |
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form lipid-binding domains called PH domains a derivative is Phosphoinositides (PI) |
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-one is calcium channel located at the surface of the smooth endoplasmic reticulum -binding of ip3 opens the channel and allows ca2+ ions to diffuse out |
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15 Regulation of blood glucose level |
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- **different stimuli acting on the same target may induce the same response -** glucagon and epinephrine bind to different receptors on the same cell -both hormones stimulate glucoses breakdown and inhibit synthesis -**cAMP is activated by the G protein of both hormone receptors (convergence) -Responses are amplified by signal cascades |
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15 other aspects of cAMP signal Transduction |
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-some PKA molecules phosphorylate nuclear proteins -phosphorlayted transcription facttors regulate gene expression -phosphatases halt the reaction cascade -cAMP is produced as long as the external stimuli is present |
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15 role of GPCRs in sensory Preception |
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Definition
-rhodopsin is a photosensitive protein for black and white vision that is also a GPCRs -sveral color recptors are GCPRs -oderant receptors in the nose are gcprs -taste receptors for bitter and sweet are gpcrs |
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15 loss of function mutation |
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Definition
result in nonfunctional signal pathways retinitis pigmentosa:lacks ability to activate g protein |
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15 gain of function mutation |
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creates a constituively activated G protein (bengin tumors,asthma blood pressure and hiv) |
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15 Protein-tyrosine kinases |
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phosphorylate tyrosine residues on target proteins. -regulate cell growth, division, differentiation, survival, and migration. |
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15 receptor protein- tyrosine kinases (RTKs) |
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cell surface receptors of the protein-tyrosine kinase family |
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-results from ligand binding -protein kinase activity is activated .tyrosine kinase phosphorylates another subunit of the receptor (autophosphorylation). . RTKs phosphorylate tyrosines within phosphotyrosine motifs |
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15 Phosphotyrosine-Dependent Protein-Protein Interactions |
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**Phoosphorylated tyrosines bind effector proteins that have SH2 domains and PTB (Phosphotyrosine Binding) domains |
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15 SH2 and PTB domain Proteins include |
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-adaptor proteins that bind other proteins -docking proteins that supply receptors with other tyrosine phosphorylation sites -signaling enzymes (kinases) that lead to changes in the cell -transcription factors |
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15 The Ras Map kinase pathway |
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-** ras Gprotein embedded in the membrane by a lipid group -Ras is active when bound to gtp and inactive when bound to GDP -ras can have GTPase activity |
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15 Accesory proteins in ras-map kinase pathway |
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Definition
GAPs- shortenn the active time of Ras GEFs-stimulate the exchange for GDp to GTP GDIs-inhibit GDP |
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15 Ras-MAP kinase cascade |
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Definition
a cascade of enzymes resulting in activating transcription factors |
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15 adapting map kinase to transmit different tyeps of information |
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Definition
-end results differ in different cells/ situations -specificity of the MAP kinase response due to differences in the types of kinases participating and differences in spatial organization of components |
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15 signaling by the the insulin receptor |
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Definition
-insulin regulates blood glucose levels by increasing cellular uptake of glucose -The insulin receptor is a proteintyrsine kinase .) autophosphorylated receptor is a protein-tyrosine kinase .) IRSs bind proteins with SH2 domains, which activate downstream signal molecules. .) SH2 domain-containg proteins are kinases that phosphorylate a lipid, PI3 kinase |
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-PKB regulates glucose uptake by GLUT4 transporters .) GLUT4 transporters reside in intracellular membrane vesicales .)Vesicles fuse with the mebrane in response to ligand binding to the IR -Diabetes mellitus is caused by defects insulin signaling and type 2 diabetes is caused by gradual insensitivity to insulin |
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15 Insulin signaling and lifespan |
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- lifespan increased with insulin decreases; shows high levels and increased insulin sensitivity |
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Signaling pathways in Plants |
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Definition
-plants lack cyclic nucleotides and RTKs -plants have protein kinases what phosphoylate histidine residues >downstream cascade simlar to Map kinase cascade >target of the cascade is usually transcription factors |
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Cytoplasmic calcium levels |
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Definition
are determined by events within a membrane -calcium levels control cistol beacause it is pumped out into the extracellular space and the membrane is highly permeable to the ion -calcium channels can be transiently opened by action potentiality or calcium itself -**calcium binds to calcium binding proteins like calmodulin which afffects other proteins |
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Regulating calcium concentration in plant cells |
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Definition
-cytosolic calcium changes in response to sever stimuli, including light, pressure, gravity, and hormones -Calcium signaling aids in decreasing turgor pressure in guard cells |
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Signaling pathways can converge, diverge, and cross talk as follows... |
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Definition
-**Signals form unrelated receptors can converge to activate a common effector -**identical signals can diverage to activate a variety of effectors -**signals can be passed back and forth between pathways as a result of crosstalk |
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- GPCRs, receptors tyrosine kinases, and integrins bind to different ligands but they all can lead to a docking site for Gbr2 |
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