4_Cell Bio 2 Flashcards
how is extracellular cell signaling elicited?
(various mechanisms)
- pathogens
- damage or contact w/ neighboring cells
- growth factors
- cytokines
- hormones
- extracellular matrix
define the following:
- paracrine
- autocrine
- endocrine
- paracrine - local effect, w/ minimal diffusion
- autocrine - molecules made/secreted w/in the cell, affecting self
- endocrine - distant effect by circulating molecule
synaptic pathway;
define
secretions of neurotransmitters by neurons –> to target cells at SYNAPTIC JUNCTIONS
receptors:
location and characteristics
- loc:
- extracellular: on cell surface
- intracellular: w/in the cell; usually *transcription factors
- characteristics
- ligands have high affinity for SPECIFIC RECEPTORS –> fits as “lock and key” to produce intracellular response
5 possible outcomes of receptor-ligand binding on
cell surfaces?
- ION CHANNEL opening (synapses)
- G-PROTEIN activation
- ENZYME activation
- PROTEOLYSIS caused by growth factor –> activating latent transcription factor
- PROTEIN CONFORMATIONAL CHANGE activation <– in response to growth factor –> activates latent transcription factor
receptors with kinase activities;
action, examples
- action:
- phosphorylate target proteins at specific amino acids
- REVERSED by phosphatases that remove the phosphate group from the protein
- examples:
- Tyrosine kinase - inhibited by many anti-cancer drugs
- Serine/threonine kinase
- Lipid kinase
describe the relationship of tyrosine kinase with signal transduction pathways
- tyrosine kinase (TK) receptors are membrane proteins *(transmembrane receptors)
- TK PHOSPHORYLATES target proteins at tyrosine sites –>
- TK induces receptor dimerization –> autophosphorylation of receptor tyrosines–>
- coupling of phosphorylated receptor to INACTIVE RAS protein bound to GDP –>
- **GTP displaces GDP –> activating RAS **–>
- RAS can activate other intracellular signaling systems via MAP kinase, PI3 kinase, and other pathways
- (e.g. Insulin Receptor, or Epidermal and Platelet-Derived growth factors)
which form of RAS is ACTIVE?
when bound to GDP or GTP?
RAS is ACTIVE when bound to triphosphate (GTP)
RAS-GTP is active form
how does negative feedback affect the signal transduction pathway?
- negative feedback of the system –>
- Active RAS hydrolyses GTP –> GDP –>
- RAS-GDP is therefore inactive
what is the effect of proteins from mutant RAS genes on the signal transduction pathway?
- proteins from mutant RAS genes –> DELAY or PREVENT GTP hydrolysis –> resulting in CONSTANT PROLIFERATIVE SIGNALING
which components of the signal transduction pathway have NO INTRINSIC CATALYTIC ACTIVITY?
what are the effects of these
These mediate a variety of protein-protein interactions
Examples:
- Immune receptors, cytokine receptor, integrins
- non-receptor tyrosine kinase: phosphorylate receptor or other proteins
- SRC (human homolog of src protein of the Rous Sarcoma Virus)
G-protein coupled receptors (GPCR):
fxn, mech, #
- fxn: mediates protein-protein interactions
- mech:
- assoc. of G-protein that contains GDP –> binds GTP
- exchange of GDP for GTP generates intracellular mediators cyclic AMP (cAMP) and inositol triphosphate
- # : 1500+ polypeptide receptors embedded in plasma membrane
nuclear receptors:
define, mechanism
- def: DNA-binding proteins involved in signal transduction pathways
- mech: can either ACTIVATE or REPRESS gene transcription
notch family receptors:
function
- involved in signal transduction pathways
- mech:
- binds ligand –> receptor cleavage –>
- translocates intracellular NOTCH protein to form –> transcription complex
Wnt protein receptors:
function, receptor proteins
- fxn: involved in signal transduction pathway
- involved in protein degradation complex via levels of intracellular Beta-catenein
- translocates intracellular B-catenin protein –>
- to form transcription complex
- receptor proteins: Frizzled, Disheveled
what are the various outcomes of protein phosphorylation?
- ENZYME activation or inactivation
- TRANSCRIPTION FACTOR localization
- TRANSCRIPTION activation or inactivation
- ACTIN polymerization or depolymerization
- PROTEIN stabilization or destabilization
- FEEDBACK LOOP activation
what are the roles of transcription factors in the signal transduction pathways?
- CONFORMATIONAL CHANGES of transcription factors
- GENE EXPRESSION activation: MYC, JUN, p53
- BIND OTHER PROTEINS using DNA-binding domains adn regions (esp RNA polymerase)
- INVOLV. W/ ENHANCERS (various expression of these)
list the actions of growth factors and receptors?
- promote entry of cells into cell cycle
- promote replication <– by unblocking cell cycle progression
- promote synthesis of molecules needed for cell dividion
- PREVENT APOPTOSIS
- possible others
epidermal growth factor (EGF) and transforming growth factor alpha
structure, fxn, pathology
- structure:
- four receptors w/ tyrosine kinase activities
- produced by macrophages and epithelial cells
- fxn:
- mitogenic for hepatocytes, fibroblasts, and many epithelail cells
- pathology:
- mutations/amplifications of receptors in human cancers –> HER2 in breast cancer
hepatocyte growth factor (HGF); aka Scatter Factor:
structure, fxn, pathology
- structure: produced by hepatic stromal cells, fibroblasts, and endothelial cells
- fxn: mitogenic for hepatocytes and many epithelial cells
- pathology:
- *stimulated by MET receptor<– which is mutated or overexpressed in many cancers
platelet-derived growth factor:
structure, fxn, receptors
- structure: family of several proteins produced by endothelial cells, platelets, macrophages, keratinocytes, and smooth muscle cells
- fxn: chemotactic and proliferative
- receptors:
- PGDF-alpha
- PGDF-beta
vascular endothelial growth factor (VEGF):
structure, fxn, ex
- structure:
- produced by mesenchymal cells
- four factors (A-D);
- **VEGF-A is MAJOR ANGIOGENIC STIMULUS
- fxn:
- increases vascular permeability
- stim proliferation of endothelial cells
- examples: placental growth factor is critical in embryonic development
which is the major angiogenic stimulus?
VEGF-A
(vascular endothelial growth factor)
fibroblast growth factor:
structure, fxn
- structure: family of 20 proteins
- fxn
- chemotactic
- stim fibroblasts, angiogenesis, and synthesis of extracellular matrix
- fxn in wound healing, development, and hematopoeisis (tissue repair after injury)
transforming growth factor Beta
(TGF-Beta)
structure, fxn,
- structure: cytokines are secreted; family of 30 proteins
- fxns: pleiotropic (multitude of effects)
- anti-inflammatory
- drives scar formation and fibrosis in various organs
- inhibits collagen degradation
- serine/threonine kinase activities activate “Smads”, w/ multiple effects
*
what are SMADS, and which growth factor are they associated with?
- SMADS are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily
- important for regulating cell development and growth
extracellular matrix:
functions
- mechanical support for cells
- control proliferation of cells
- structure for tissue renewal (e.g. in liver)
- establish microenvironments for specific tissues
- **CONSTANTLY IN FLUX; remodeling is a major characteristic
interstitial matrix:
found where, define, contains..
- found in extracellular matrix
- def: gel b/w cells; contains multiple major constituents
- contains
- collagens
- fibronectin
- elastin – provides elastic layers in arteries
- proteoglycans
- hyaluronate
basement membrane:
define, organization, contents
- def: porous flat membrane
- organization: organized around epithelial, smooth muscle, mesenchymal and endothelial cells
- contents: major proteins (laminin, type IV collagen)
what are the components of the extracellular matrix?
- structural proteins; elastins and collagens
- water-hydrated gels; proteoglycans, hyaluronan
- adhesive glycoproteins
collagen:
types
30 types of collagen
- Fibrillar collagens: major part of all connective tissues; triple helices, vitamin C-dependent
- Non-fibrillar collagens: involved in basement membrane structure
elastin:
use
- associated w/ fibrillin
- important in large arteries, cardiac valves, skin, ligaments, and uterus
what is the difference b/w glycosaminoglycans and hyaluronan?
- glycosaminoglycans: long chains of proteoglycans; hydrated compressible gels in joints
- hyaluronan: high molecular weight polymer of hyaluronic acid linked to glycosaminoglycans; found in extracellular matrix; esp in soft tissues
what are the 3 key adhesive glycoproteins/receptors?
- fibronectin: a large glycoprotein synthesized by a variety of cells; differing domains that bind other proteins
- laminin: large glycoprotein, major membrane component; binds other proteins; role in cell proliferation and differentiation
- integrins: attaches cells to fibronectin and laminin; various roles in many processes
cell cycle:
regulation and purpose
- regulated by activators and inhibitors
- required for steady state tissue homeostasis
cell cycle:
what is the purpose of cyclins and CDK inhibitors?
- progression of cell cycles driven by cyclins and cyclin-dependent kinases (CDKs)
- 15 cyclins; *(sequence of cyclin D, E, A, and B in cell division)
- CDK inhibitors: enforces cell cycle checkpoints by inhibition of cyclin-dependent kinases (CDKs)
stem cell:
fxn, and describe the division
- fxn: self-renewing –> maintain constant numbers
- division
- **asymmetric division leads one daughter cell into a differentiation pathway while the other remains a stem cell
what are the 2 key types of stem cells;
and how are they related to regenerative medicine
-
embryonic SCs: UNDIFFERENTIATED, totipotent;
- differentiation can be induced under culture conditions
-
tissue SCs (adult SCs): produces ONLY normal constituents of that particular tissue
- protected in stem cell niches w/in tissues
- regenerative medicine involves introducing and integrating stem cells w/ the goal of restoration of damaged tissue to its pristine condition
