Lecture 19 - quiz 2 Flashcards

1
Q

describe cell communication

A

Fundamental biological process that is of particular importance in multicellular organisms

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2
Q

what is cell communication necessary for

A

Necessary for growth, migration, and differentiation of cells in the embryo and their tissue organisation

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3
Q

describe cell communication in adults

A

orchestrate normal cellular behavior but also for responses to wounding and infection

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4
Q

what can defects in cell communication cause

A

cancer, diabetes and disorders of the immune and cardiovascular system.

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5
Q

name and describe cell interactions - gen

A

cell produces a factor –> travels to another cell –> binds to receptor –> signal transduction in target cell and some effect

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6
Q

describe steps of cellular interactions - 4

A
  1. Production of signalling molecule.
  2. Activation of the receptor.
  3. Biochemical changes resulting in signal transduction.
  4. Signal sent to nucleus to affect gene expression (in many cases)
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7
Q

how are growth factors/hormones/survival factors (ligands) classified

A

according to distance over which they act

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8
Q

what is autocrine

A

same cell

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9
Q

what is paracrine

A

close proximity

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10
Q

what is endocrine

A

at a distance (like hormone through bloodstream)

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11
Q

what is snyaptic

A

specific to nerve cells

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12
Q

what is juxtacrine

A

direct contact
mostly in brain

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13
Q

what is each cell programmed to do

A

respond to specific combo of ligands
if no survival or growth factor = programmed cell death

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14
Q

describe combinatorial signalling

A

Cells are exposed to many ligands
Cells must only respond to some of them
Most cells must depend on a set of ligands to avoid programmed cell death
need factors to survive and grow and proliferate

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15
Q

can the same ligand induce diff results in target cells

A

yesss
the ligand binds to diff receptors
the same receptor elicit diff responses

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16
Q

explain how the same ligand induce diff results in target cells

A

ligands act at low concentration and they are recognized by their receptor with high affinity
effect depends on receptor and cell type
ex: skeletal muscle with ach = contract but heart muscle wit ach = relax, secretory cell with ach= secretion

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17
Q

what do ligands bind to

A

Specific receptors

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18
Q

describe hydrophilic and liposoluble ligands

A

Hydrophilic ligands (cannot cross through membrane) have transmembrane receptors
Small liposoluble ligands have to cross the membrane to reach an intracellular receptor.

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19
Q

describe cell surface receptors

A

transmembrane receptors
Receives signal and transmits to other side

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20
Q

describe intracellular receptors

A

mostly hormones = can enter cell by themselves - lipophilic - hydrophobic

21
Q

describe receptors for liposoluble steroid hormones

A

Are Not Cell Surface Receptors but Are Localised in the Cytoplasm or Nucleus and Act to Directly Regulate Gene Expression.

22
Q

how do small hydrophobic molecules get into a cell

A

Small hydrophobic molecules like steroids diffuse through cell membrane of target cells
Inside the cell they bind to intracellular receptors and activate them
These receptors (member of steroid nuclear Receptor family) then directly regulate gene transcription
many diff drugs made for these receptors

23
Q

describe intracellullar receptor superfamily

A

now have transcription factor and regulated by ligand, hormone binds = induce transcription or genes important for action of hormones
all have dna binding domain = looks similar but binds diff promoters and hormone binding domain = diff for each

24
Q

describe ligands that bind to cell surface receptors

A

Hydrophilic and Can Not Pass Through the Plasma Membrane.

25
Q

describe hydrophilic ligands

A

Frequently small molecules like neurotransmitters
most growth factors are small proteins
peptides - 6-20kda in size
but some growth factors = large proteins like 90kda hepatocyte growth factor (hard to mimic since cannot pass pm, must inject into bloodstream)

26
Q

name 3 classes of cell surface receptors

A

ion channel linked
g protein linked
enzyme linked

27
Q

describe ion channel linked receptor

A

Ligand open or close ion channel
Involved rapid synaptic signaling
ligand binds and change conformation and ions can go in or out - changes structure

28
Q

describe g protein linked receptor

A

Use trimeric G protein as an intermediate to regulate activity of another membrane bound molecule
inside = g protein changes when ligand binds and becomes enzyme or ion channel
kinase usually phosphorylated something to be active = more complicated

29
Q

describe enzyme linked receptor

A

Have enzymatic activity or are associated with enzymes when activated
extracellular domain, tm domain and intracellular domain
binds ligand and enzymatic activity = kinase, phosphorylates something here

30
Q

name 4 classes of enzyme coupled receptors

A
  1. Receptor tyrosine kinases
  2. Receptor tyrosine kinase associated receptors
  3. Receptor serine/threonine kinases
  4. Receptor tyrosine phosphatases
31
Q

describe six subfamilies of receptor tyrosine kinases

A

epidermal growth factor receptor
insulin receptor
nerve growth factor receptor
platelet derived growth factor
fibroblast growth factor
vascular endothelial growth factor
Intracellular domain = all tyrosine kinases so looks something, surrounding sequences makes kinase specific
extracellular domain = all diff since binds to diff kinase

32
Q

what are many receptors for growth and differentiation factors

A

Transmembrane Receptor Tyrosine Specific Protein Kinases

33
Q

name and describe 3 domains in receptor tyrosine kinase

A
  1. Extracellular domain: large and glycosylated, binds to the growth factor.
  2. Transmembrane domain: short and composed of hydrophobic amino acids
  3. Intracellular domain: contains the catalytic kinase domain.
34
Q

describe structure of a few protein kinases

A

SRC tyrosine kinase - no extracellular domain
most have just intracellular
tgf-beta receptor = not just intracellular

35
Q

How Does the Binding of a Protein to the Extracellular Portion of a Receptor Tyrosine Kinase Regulate the Catalytic Domain on the Other Side of the Protein? - 4

A
  1. Growth factor binding cause receptor tyrosine kinase dimerization.
  2. Dimerization causes transphosphorylation of receptors (brings 2 subunits together)
  3. Phosphotyrosines act as docking sites for SH2 containing proteins (specifically binds to phosphorylated tyrosine)
  4. Some of those
    are themselves
    phosphorylated
    by the receptor.
36
Q

How Does the Binding of a Protein to the Extracellular Portion of a Receptor Tyrosine Kinase Regulate the Catalytic Domain on the Other Side of the Protein? - gen

A

diff for each receptor - kinase gives specificity, intracellular domain have diff sequence next to kinase domain
some have sh3 domains = bond to polyprolines
autophosphorylate each other - specific for each kinase

37
Q

describe SH2 and SH3 domains

A

small protein modules
function = recognize specific aas in their target proteins
SH2 and SH3 composed of approximately 100 and 50 aa respectively
SH2 and SH3 are Src homology regions 2 and 3
They are usually shared by the various intracellular substrates of RTKs (which have otherwise diverse structures and functions
binds to phosphotyrosines - small regions, increase on intracellular path of receptor tyrosine kinase

38
Q

describe substrates for receptor tyrosine kinases

A

Contain SH2 Domains and Recognise Phosphotyrosine Residues
do not bind to inactive receptor
some have enzymatic activity
others only act to recruit signalling molecules

39
Q

what does sh2 and sh3 domains do

A

sh2 to bind phosphorylated receptor
sh3 domain to bind protein
forms complex

40
Q

describe phosphorylation sites of a receptor

A

only specific tyrosine residues in a receptor are phosphorylated
creates binding sites for specific substrates
not all receptors have same substrate
diff tyrosines bind diff receptors when phosphorylated
inside = kinase domain, diff phosphates on tyrosines

41
Q

where is the specificity of the receptor to activate signalling pathways

A

the specificity of the receptor to activate signaling pathways is built into its primary sequence

42
Q

what does RAS protein do

A

Provide a Crucial Link in the Intracellular Signaling Cascades Activated by Receptor Tyrosine Kinases.

43
Q

descrive RAS protein

A

Ras is a monomeric GTPase
– Bound to GTP: active
– Bound to GDP: inactive
* Sos activates Ras by promoting GDP release
– GTP:GDP ratio is 10:1 in cells
* GTPase activating proteins enhance Ras GTPase activity
– GTP ® GDP, (Ras inactivation)

44
Q

describe how ras protein helps relay signals from receptor tyrosine kinases to nucleus to help stimulate cell proliferation or differentiation

A

A cascade is formed as each protein activates a downstream molecule.
Signal generated by: Phosphorylation = Tyrosine and Serine threonine
GTP binding
downstream = kinases or phosphatases

45
Q

describe relay of signals from activated receptor tyrosine kinases to nucleus

A

raf = ser/thre kinase –> mek phosphorylation –> mapk = now active so kinase cascade, until signals in nucleus (so phosphorylated then active)
sos = bind to receptor, pushes to inactive form and reverse

46
Q

describe what happens when things go wrong in relay of signals

A

over production of ligand or mutation in receptor (so always on)
in cancer = cannot bind ligand so always on
ras mutation so always active (also in all kinases)
hard to treat cancer since do not know where problem in cascade pathway is

47
Q

describe protein tyrosine phosphatases

A

Because phosphorylation is basically unidirectional, another enzyme (called a protein phosphatase) is needed to remove it
ptp = protein tyrosine phosphatase

48
Q

describe diversity of protein tyrosine phosphatases

A

non transmembrane ptps = inside cell, swims around
receptor type ptps = some tm intracellular domain = phosphate, and extracellular domain binds ligand
cdc25 = can do both ser, threo tyrosine
pten = deals with lipids