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Y1 - Pathology > 4_Cell Bio 2 > Flashcards

4_Cell Bio 2 Flashcards

1
Q

how is extracellular cell signaling elicited?

(various mechanisms)

A
  • pathogens
  • damage or contact w/ neighboring cells
  • growth factors
  • cytokines
  • hormones
  • extracellular matrix
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2
Q

define the following:

  • paracrine
  • autocrine
  • endocrine
A
  • paracrine - local effect, w/ minimal diffusion
  • autocrine - molecules made/secreted w/in the cell, affecting self
  • endocrine - distant effect by circulating molecule
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3
Q

synaptic pathway;

define

A

secretions of neurotransmitters by neurons –> to target cells at SYNAPTIC JUNCTIONS

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4
Q

receptors:

location and characteristics

A
  • 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
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5
Q

5 possible outcomes of receptor-ligand binding on

cell surfaces?

A
  1. ION CHANNEL opening (synapses)
  2. G-PROTEIN activation
  3. ENZYME activation
  4. PROTEOLYSIS caused by growth factor –> activating latent transcription factor
  5. PROTEIN CONFORMATIONAL CHANGE activation <– in response to growth factor –> activates latent transcription factor
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6
Q

receptors with kinase activities;

action, examples

A
  • 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
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7
Q

describe the relationship of tyrosine kinase with signal transduction pathways

A
  1. tyrosine kinase (TK) receptors are membrane proteins *(transmembrane receptors)
  2. TK PHOSPHORYLATES target proteins at tyrosine sites –>
  3. TK induces receptor dimerization –> autophosphorylation of receptor tyrosines–>
  4. coupling of phosphorylated receptor to INACTIVE RAS protein bound to GDP –>
  5. **GTP displaces GDP –> activating RAS **–>
  6. 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)
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8
Q

which form of RAS is ACTIVE?

when bound to GDP or GTP?

A

RAS is ACTIVE when bound to triphosphate (GTP)

RAS-GTP is active form

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9
Q

how does negative feedback affect the signal transduction pathway?

A
  1. negative feedback of the system –>
  2. Active RAS hydrolyses GTP –> GDP –>
  3. RAS-GDP is therefore inactive
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10
Q

what is the effect of proteins from mutant RAS genes on the signal transduction pathway?

A
  • proteins from mutant RAS genes –> DELAY or PREVENT GTP hydrolysis –> resulting in CONSTANT PROLIFERATIVE SIGNALING
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11
Q

which components of the signal transduction pathway have NO INTRINSIC CATALYTIC ACTIVITY?

what are the effects of these

A

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)
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12
Q

G-protein coupled receptors (GPCR):

fxn, mech, #

A
  • fxn: mediates protein-protein interactions
  • mech:
    1. assoc. of G-protein that contains GDP –> binds GTP
    2. exchange of GDP for GTP generates intracellular mediators cyclic AMP (cAMP) and inositol triphosphate
  • # : 1500+ polypeptide receptors embedded in plasma membrane
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13
Q

nuclear receptors:

define, mechanism

A
  • def: DNA-binding proteins involved in signal transduction pathways
  • mech: can either ACTIVATE or REPRESS gene transcription
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14
Q

notch family receptors:

function

A
  • involved in signal transduction pathways
  • mech:
    • binds ligand –> receptor cleavage –>
    • translocates intracellular NOTCH protein to form –> transcription complex
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15
Q

Wnt protein receptors:

function, receptor proteins

A
  • 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
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16
Q

what are the various outcomes of protein phosphorylation?

A
  • ENZYME activation or inactivation
  • TRANSCRIPTION FACTOR localization
  • TRANSCRIPTION activation or inactivation
  • ACTIN polymerization or depolymerization
  • PROTEIN stabilization or destabilization
  • FEEDBACK LOOP activation
17
Q

what are the roles of transcription factors in the signal transduction pathways?

A
  • 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)
18
Q

list the actions of growth factors and receptors?

A
  1. promote entry of cells into cell cycle
  2. promote replication <– by unblocking cell cycle progression
  3. promote synthesis of molecules needed for cell dividion
  4. PREVENT APOPTOSIS
  5. possible others
19
Q

epidermal growth factor (EGF) and transforming growth factor alpha

structure, fxn, pathology

A
  • 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
20
Q

hepatocyte growth factor (HGF); aka Scatter Factor:

structure, fxn, pathology

A
  • 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
21
Q

platelet-derived growth factor:

structure, fxn, receptors

A
  • 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
22
Q

vascular endothelial growth factor (VEGF):

structure, fxn, ex

A
  • 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
23
Q

which is the major angiogenic stimulus?

A

VEGF-A

(vascular endothelial growth factor)

24
Q

fibroblast growth factor:

structure, fxn

A
  • 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)
25
Q

transforming growth factor Beta

(TGF-Beta)

structure, fxn,

A
  • 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
      *
26
Q

what are SMADS, and which growth factor are they associated with?

A
  • SMADS are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily
  • important for regulating cell development and growth
27
Q

extracellular matrix:

functions

A
  • 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
28
Q

interstitial matrix:

found where, define, contains..

A
  • found in extracellular matrix
  • def: gel b/w cells; contains multiple major constituents
  • contains
    • collagens
    • fibronectin
    • elastin – provides elastic layers in arteries
    • proteoglycans
    • hyaluronate
29
Q
A
30
Q

basement membrane:

define, organization, contents

A
  • def: porous flat membrane
  • organization: organized around epithelial, smooth muscle, mesenchymal and endothelial cells
  • contents: major proteins (laminin, type IV collagen)
31
Q

what are the components of the extracellular matrix?

A
  • structural proteins; elastins and collagens
  • water-hydrated gels; proteoglycans, hyaluronan
  • adhesive glycoproteins
32
Q

collagen:

types

A

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
33
Q

elastin:

use

A
  • associated w/ fibrillin
  • important in large arteries, cardiac valves, skin, ligaments, and uterus
34
Q

what is the difference b/w glycosaminoglycans and hyaluronan?

A
  • 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
35
Q

what are the 3 key adhesive glycoproteins/receptors?

A
  • 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
36
Q

cell cycle:

regulation and purpose

A
  • regulated by activators and inhibitors
  • required for steady state tissue homeostasis
37
Q

cell cycle:

what is the purpose of cyclins and CDK inhibitors?

A
  • 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)
38
Q

stem cell:

fxn, and describe the division

A
  • fxn: self-renewing –> maintain constant numbers
  • division
    • **asymmetric division leads one daughter cell into a differentiation pathway while the other remains a stem cell
39
Q

what are the 2 key types of stem cells;

and how are they related to regenerative medicine

A
  • 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

Y1 - Pathology (14 decks)

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