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Biochemistry - HBF1 > Lecture 05 > Flashcards

Lecture 05 Flashcards

(60 cards)

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1
Q

What is signal transduction?

A

Transmission of molecular signals from a cell’s exterior to its interior

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2
Q

After a response is initiated as a result o signal transduction, how can it be stopped?

A

Either the signaling molecule:receptor complex is disrupted or the triggered event is disrupted.

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3
Q

Name the 4 forms of cell signaling?

A

Endocrine, paracrine, autocrine, juxtacrine

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4
Q

Define endicrine signaling

A

Secreted molecules travels to the target cell via the bloodstream

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5
Q

Define paracrine signaling

A

Secreted molecule diffuses to a nearby target cell of a different type

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6
Q

Define autocrine signaling

A

Secreting cells are themselves the target of the signaling molecule

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7
Q

Define juxtacrine signaling

A

Secreted molecule remains attached to signaling cell; direct contact

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8
Q

How do lipophilic signaling molecules induce a response?

A

They are membrane permeable and bind an intracellular receptor

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9
Q

How do hydrophilic signaling molecules induce a response?

A

They are not membrane permeable and bind to a cell surface receptor

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10
Q

How to lipophilic signaling molecules travel in the bloodstream?

A

They are bound to carrier proteins

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11
Q

What are the two major classes of cell surface receptors?

A

G-Protein Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs)

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12
Q

What are examples of GPCRs?

A

alpha- and beta-andrenergic receptors, rhodopsin

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13
Q

What is the structure of all members of the GPCR family?

A

7 transmembrane helices (serpentine pattern)

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14
Q

How do GPCR members exert their effects inside the cell?

A

Heterotrimeric G-proteins

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15
Q

Name the subunits of G-proteins

A

alpha (binds guanine nucleotide), beta, and gamma

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16
Q

Of the 3 subunits of a G-protein, which contain a lipid tail for association with the plasma membrane?

A

Alpha and gamma

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17
Q

Name the two states of the G-alpha subunit

A

GDP-bound inactive, GTP-bound active

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18
Q

Describe the steps of the G-Protein activity cycle

A
  1. GDP-bound G-alpha forms a stable complex with beta and gamma
  2. Guanine-nucleotide exchange factors (GEF) bind to G-alpha and exchanges GDP for GTP
  3. Activated G-alpha dissociates from the trimeric complex and binds target protein to initiate a response to the signal
  4. G-alpha is deactivated by hydrolysis of bound GTP.
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19
Q

How exactly is G-alpha deactivated?

A

Normal GTPase activity is low. GTPase activating proteins (GAPs) bind to G-alpha to accelerate the rate of GTP hydrolysis and stop the reponse to the signal

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20
Q

Name the 4 different types of G-alpha subunits

A

Gs, Gi, Gq, Gt

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21
Q

What type of receptor does G-alpha s containing G-proteins associate with?

A

beta-andrenergic receptors

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22
Q

How does the G-alpha s subunit induce a response?

A

G-alpha s activates adenylate cyclase and increases the concentration of cAMP. This activates protein kinase A which then phosphorylates its protein targets

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23
Q

What type of receptor does G-alpha i containing G-proteins associate with?

A

alpha-2 adrenergic receptors

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24
Q

How does the G-alpha i subunit induce a response?

A

It binds to and inhibits adenylate cyclase, which lowers cAMP concentration. This deactivates protein kinase A

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25
What type of receptor does G-alpha q containing G-proteins associate with?
alpha-1 andrenergic receptors
26
How does the G-alpha q subunit induce a response?
It binds to and activates phospholipase C (PLC). This will cleave PIP2 to produce diacylglycerol and inositol triphosphate. IP3 then diffuses into the endoplasmuc/sarcoplasmic reticulum) and release calcium ions into the cytoplasm. Calcium ions activate protein kinase C
27
What needs to bind to PKC before it is fully activated?
Both a calcium ion and diacylglycerol
28
When does diacylglycerol bind to PKC?
After the PKC:calcium ion complex has associated with the plasma membrane
29
How is PIP2 generated?
2 successive phosphorylations of PI
30
What is a targeted approach to eliminate signaling through G-alpha s?
cAMP cleavage with cAMP phosphodiesterase
31
Where is G-alpha t found and what is its role?
In the retina; it is the transducer of light stimulus for sight
32
What is the name used to refer to a G-protein that contains a G-alpha t subunit?
Transducin
33
What GPCR in the cytoplasm does transducin associate with?
Rhodopsin
34
How does the G-alpha t subunit induce a response?
It binds and activates cGMP phosphodiesterase (PDE), which lowers the concentration of cGMP. This closes cGMP-gated ion channels, resulting in hyperpolarization of the membrane and response by the optic nerve
35
How does rhodopsin activate G-alpha t?
Retinal (cofactor of rhodopsin) absorbs a photon and causes a conformation change in the protein that in turn activates G-alpha t.
36
What are the primary features of Receptor Tyrosine Kinases (RTKs)?
They function as dimers and have a tripartite structure
37
Describe the 3 parts of an RTK
A. an extracellular domain that binds the signaling molecule B. a transmembrane segment C. an intracellular tyrosine protein kinase domain
38
For RTKs, list the two types of intracellular tyrosine kinase domains
Self-encoded (intragenic) or the product of another gene that binds to the cytoplasmic RTK and exerts kinase effect (extragenic)
39
What do many RTKs use to exert their effects in the cell?
Ras family of small G-proteins related to G-alpha subunits
40
Give an example of a protein with an extragenic tyrosine kinase
Growth hormone receptor (GHR)
41
What is the name of the monomeric tyrosine kinase that GHR couples with?
JAK2
42
How many GHR:JAK2 complexes bind to one molecule of growth hormone?
2; a dimer
43
How does the GHR:JAK2 dimer come together?
Cross-phosphorylation of opposing JAK2 followed by each JAK2 phosphorylating Tyr residues on their respective GHR domains
44
What are 2 examples of proteins with an intragenic tyrosine kinase?
Epidermal growth factor receptor (EGFR) and insulin receptors
45
What structural features of EGFR ses it apart from GHR?
It always exists as a dimer in the membrane; the unbound dimer is not catalytically active, unlike GHR
46
How does the binding of epidermal growth factor activate the EGFR dimer?
Binding induces a conformational chnge in the cytoplasmic dmain of the receptor, which activates tyrosine kinase activity
47
What is the ratio of EGFR to EGF?
2 hormone molecules per dimer
48
What is the GEF for Ras?
Sos
49
How does Ras protein signaling begin?
The SH2 domain of the adaptor protein Grb-2 binds to phosphorylated tyrosines in EGFR. Then, the SH3 domain bonds to Sos, which then activates Ras by swapping GDP for GTP
50
What does Ras initiate?
Ras initiates activation of the mitogen-activated protein kinase pathway (MAPK)
51
What does the MAPK pathway help with?
Cell proliferation, gene expression, differentiation, mitosis, and apoptosis
52
Describe the structure of the dimeric insulin receptor
Contains an extracellular ligand binding domain (alpha) and an intracellular tyrosine kinase domain (beta)
53
What happened after the imeric insulin receptor is assembled?
Each polypeptide is cleaved by a protease internally, leavint both domain joined by disulfide bonds.
54
What activates Tyr kinase activity in the insulin receptor?
The binding of insulin
55
What happens after insulin is bound to the receptor?
First, the receptor autophosphorylates. Then, insulin receptor substrate (IRS-1) binds to the phosphorylated intracellular domain and gets phosphorylated. This starts the effects of insulin in the cell
56
After IRS-1 is phosphorylates, what are two methods of insulin signaling?
Through Ras or through PIP3/PKB
57
Describe insulin signaling through Ras
SH2 domain of adaptor protein Grb-2 binds to phosphotyrosines in IRS-1 and SH3 domain binds to Sos. Sos activates Ras, which activates the MAPK pathway.
58
How does the MAPK pathway respond to insulin?
There will be increased transcription of genes coding for enzymes of pathways involved in energy storage (glycogen synthesis, tryacylglycerol synthesis)
59
Describe insulin signaling through PIP3/PKB
PIP3 is synthesized by phosphorylating PIP2. PIP3 then activates protein kinase B
60
How does PKB act in response to insulin?
Activation of glycogen synthase and increase GLUT4 (glucose transporter) movement to plasma membrane

Biochemistry - HBF1 (5 decks)

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