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Anat 212 > Ligands and Receptors > Flashcards

Ligands and Receptors Flashcards

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1
Q

Cell communication

A

-only in multicellular organisms

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2
Q

Cell communication in embryos?

A

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

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3
Q

Cell communication in adults?

A

Helps with normal ceullar behaviour but also responses to wounding and infection

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4
Q

Defects in cell communication can lead to ?

A

-Cancer
-Diabetes
-Disorders of the immune system
-Disorders of the CV system

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5
Q

Cellular interactions steps?

A
  1. Production of signalling molecule
  2. Activation of the receptor on the other cell
  3. Biochemical changes resulting in signal transduction
  4. Signal sent to nucleus to affect gene expression
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6
Q

Examples of ligands?

A

-Growth factors
-Hormones

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7
Q

Autocrine signalling?

A

When the ligand acts on the same cell

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8
Q

Paracrine signalling?

A

When the ligand acts on another cells close in proximity

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9
Q

Endocrine signalling?

A

When the ligand acts at a distance
Ex. Hormones travel through the bloodstream

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10
Q

Synaptic signalling?

A

Specific to nerve cells

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11
Q

Juxtacrine signalling?

A

Direct signalling between neighbouring cells

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12
Q

Each cell is programmed to respond to specific combinations of ligands?

A

Combinatorial signalling
cells are exposed to many ligands
-Cells must only respond to some of them

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13
Q

How do cells avoid programmed cell death?

A

Cells rely on a set of ligands to avoid programmed cell death

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14
Q

T/F: Every cell is programmed to die unless you give it survival factors, growth factors and mitogens?

A

True

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15
Q

How can the same ligand induce different responses in different cells?

A

-The ligand binds different receptors on different cells
-The same receptor can potentially elicit different responses on different cells

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16
Q

How does ACh ligand induce different responses in target cells?

A
  1. Skeletal muscle cells: when ACh binds receptor it leads to contraction of SM
  2. Heart muscle: when ACh binds receptor it leads to relaxation of heart muscle cells
  3. Secretory cells: when ACh binds receptor it leads to secretion
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17
Q

T/F: Ligands act at low concentration and they are recognized by their receptor with high affinity?

A

True

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18
Q

Hydrophilic ligands?

A

-Cannot cross through the cell membrane
-Must bind transmembrane receptors

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19
Q

Small liposoluble ligands?

A

-Can cross through the cell membrane
-Have intracellular receptors

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20
Q

Two types of receptors?

A
  1. Surface receptors
  2. Intracellular receptors
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21
Q

Surface receptors?

A

-Recieve signals from protein-like molecules or small molecules
-Hydrophilic ligands

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22
Q

Intracellular receptors?

A

-Hydrophobic molecules that can cross the lipid membrane bind to these receptors
Ex. Vitamins/hormones

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23
Q

Liposoluble steroid hormones?

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A

-Small hydrophobic molecules that can diffuse through the cell membrane and bind intracellular receptors activating them

24
Q

Steroid nuclear receptors?

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A

-Localised in the nucleus and directly regulate the transcription of genes when bound by ligand

25
Intracellular receptor superfamily?
-All have a DNA-binding domain and are thus TFs -When bound by steroid hormone or other liposoluble molecule receptor becomes activated and transcribes genes in the nucleus
26
Cell surface ligands that are hydrophilic?
-Frequently small molecules like neurotransmitters -Growth factors (small proteins)
27
T/F: Most growth factors are small proteins?
True, hoever some can be very large proteins such as the hepatocyte growth factor which is 90 kDa
28
3 classes of cell surface receptors?
1. Ion channel linked 2. G protein linked 3. Enzyme linked
29
Ion channel linked cell surface receptors?
1. Hydrophilic ligand binds to the outside of the receptor 2. Binding leads to the opening/closing of the ion channel -These are involved in rapid synaptic signaling
30
G protein linked cell surface receptors?
1. Ligand binds to the outside of the receptor which causes a conformation change 2. Conformation change causes the receptor to bind a G-protein which activates an enzyme/ion channel
31
Enzyme linked cell surface receptors?
1. Ligand binds to the receptor this activates a catalytic domain in the cell to transmit a signal 2. These have enzymatic activity or are associated with enzymes when activated
32
Four classes of enzyme coupled receptors?
1. Receptor tyrosine kinases 2. Receptor tyrosine kinase associated receptors 3. Recetpro serine/threonine kinases 4. Receptor tyrosine phosphatases
33
Enzyme linked cell surface receptors all have?
Tyrosine kinase domains
34
T/F: Many receptors for growth and differentiation factors are transmembrane receptor tyrosine specific protein kinases?
True
35
3 Domains in receptor tyrosine kinases?
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(contains ATP which is hydrolyzed to add phosphosphate to substrate)
36
Tyrosine-Specific protein kinases?
Involved in transmission from outside the cell to inside
37
Serine/threonine-specific protein kinases?
Involved in intracellular signalling(no transmembrane/extracellular domains)
38
How does binding of a protein to the extracellular domain of a receptor tyrosine kinase regulate catalytic domain on the other side?
1. Growth factor binding causes the receptor tyrosine kinase dimerization 2. Dimerization causes phosphorylation of tyrosines on the receptor intracellularly 3. Phosphotyrosines act as docking sites for SH2 containing proteins 4. Some of those are themselves phosphorylated by the receptor and these transmit the signal
39
SH2/SH3?
Small protein molecules that bind phosphotyrosines on receptors and this protein-protein interaction transmits the signal
40
T/F: Substrates for receptor tyrosine kinases contain SH2 domains and recognise phosphotyrosines?
True
41
Substrates of RTKs?
-Don't bind inactive receptors(must be phosphorylated and bound by SH2) -Some have enzymatic activity -Others only act to recruit other signaling molecules -Make signalling specific for one receptor
42
T/F: The phosphorylation sites of the RTK determine which substrates bind?
True
43
Specific binding of susbtrates to RTKs?
-Only specific tyrosines are phosphorylated in a receptor which creates binding sites for specific substrates -Not all receptors have the same substrates
44
T/F: The specificity of the receptor to activate signaling pathways is built into its primary sequence?
true
45
Ras proteins and signaling cascades activated by RTKs?
Ras proteins link the intracellular signaling cascades activated by RTKs
46
Ras ?
-Monomeric GTPase -Bound to GTP: active -Bound to GDP : inactive
47
Sos?
GEF that activates Ras by stimulating release of GDP and binding of GTP
48
GTP: GDP ratio in cells?
10:1
49
GTPase activating proteins?
Enhance Ras GTPase activity
50
Ras-GTP
Active form of Ras, binding site of Ras is exposed which can lead to the binding of other molecules and signal transmission
51
Ras GTPase in cancer cells?
Ras is permanently active even without GTP which is constantly signaling cell proliferation/differentiation
52
How does the Ras protein help stimulate cell proliferation or differentiation?
Ras protein becomes turned on and signas from receptor tyrosine kinases to the nucleus to help with proliferation or differentiation
53
How can Ras be activated?
1. Phosphorylation of Ras 2. GTP binding to Ras
54
Relay of signals from activated receptor to the nucleus?
1. Ligand binds the receptor activating it 2. Receptor kinase domains become phosphorylated 3. Phosphorylated domains activate Sos activity 4. Sos is a GEF that activate Ras 5. Ras-GTP then activates Raf 6. Raf activates MEK which activaes MAP kinase 7. MAP kinase enters the nucleus and activates transcription of genes for proliferation
55
Protein Tyrosine Phosphatases?
Since phosphorylation is unidirectional another enzyme is needed to remove it. This inactivate the receptor tyrosine kinase
56
T/F: There are a variety of protein tyrosine phosphatases?
True

Anat 212 (23 decks)

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