Lecture 19 - quiz 2

Question 1

describe cell communication

Answer 1

Fundamental biological process that is of particular importance in multicellular organisms

Question 2

what is cell communication necessary for

Answer 2

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

Question 3

describe cell communication in adults

Answer 3

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

Question 4

what can defects in cell communication cause

Answer 4

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

Question 5

name and describe cell interactions - gen

Answer 5

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

Question 6

describe steps of cellular interactions - 4

Answer 6

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)

Question 7

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

Answer 7

according to distance over which they act

Question 8

what is autocrine

Answer 8

same cell

Question 9

what is paracrine

Answer 9

close proximity

Question 10

what is endocrine

Answer 10

at a distance (like hormone through bloodstream)

Question 11

what is snyaptic

Answer 11

specific to nerve cells

Question 12

what is juxtacrine

Answer 12

direct contact
mostly in brain

Question 13

what is each cell programmed to do

Answer 13

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

Question 14

describe combinatorial signalling

Answer 14

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

Question 15

can the same ligand induce diff results in target cells

Answer 15

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

Question 16

explain how the same ligand induce diff results in target cells

Answer 16

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

Question 17

what do ligands bind to

Answer 17

Specific receptors

Question 18

describe hydrophilic and liposoluble ligands

Answer 18

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

Question 19

describe cell surface receptors

Answer 19

transmembrane receptors
Receives signal and transmits to other side

Question 20

describe intracellular receptors

Answer 20

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

Question 21

describe receptors for liposoluble steroid hormones

Answer 21

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

Question 22

how do small hydrophobic molecules get into a cell

Answer 22

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

Question 23

describe intracellullar receptor superfamily

Answer 23

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

Question 24

describe ligands that bind to cell surface receptors

Answer 24

Hydrophilic and Can Not Pass Through the Plasma Membrane.

Question 25

describe hydrophilic ligands

Answer 25

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)

Question 26

name 3 classes of cell surface receptors

Answer 26

ion channel linked
g protein linked
enzyme linked

Question 27

describe ion channel linked receptor

Answer 27

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

Question 28

describe g protein linked receptor

Answer 28

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

Question 29

describe enzyme linked receptor

Answer 29

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

Question 30

name 4 classes of enzyme coupled receptors

Answer 30

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

Question 31

describe six subfamilies of receptor tyrosine kinases

Answer 31

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

Question 32

what are many receptors for growth and differentiation factors

Answer 32

Transmembrane Receptor Tyrosine Specific Protein Kinases

Question 33

name and describe 3 domains in receptor tyrosine kinase

Answer 33

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.

Question 34

describe structure of a few protein kinases

Answer 34

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

Question 35

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

Answer 35

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.

Question 36

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

Answer 36

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

Question 37

describe SH2 and SH3 domains

Answer 37

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

Question 38

describe substrates for receptor tyrosine kinases

Answer 38

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

Question 39

what does sh2 and sh3 domains do

Answer 39

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

Question 40

describe phosphorylation sites of a receptor

Answer 40

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

Question 41

where is the specificity of the receptor to activate signalling pathways

Answer 41

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

Question 42

what does RAS protein do

Answer 42

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

Question 43

descrive RAS protein

Answer 43

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)

Question 44

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

Answer 44

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

Question 45

describe relay of signals from activated receptor tyrosine kinases to nucleus

Answer 45

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

Question 46

describe what happens when things go wrong in relay of signals

Answer 46

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

Question 47

describe protein tyrosine phosphatases

Answer 47

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

Question 48

describe diversity of protein tyrosine phosphatases

Answer 48

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