Term
| What is the def of signal transduction? |
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Definition
| Signal Transduction = cell converts extracellular signals into intracellular events |
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Term
| What are the 2 second messengers of th GPCR signalling pathway? |
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Definition
1. cAMP as 2nd messenger
(effector protein= adenyl cyclase)
2. DAG & IP3 as 2nd messengers
(effector protein= phospholpase C; PLC) |
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Term
| Where does cAMP bind and then what happens to the PKA? What is PKA? |
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Definition
cAMP binds regulatory subunit of PKA. Causes activation of PKA catalytic subunit to phosphorylate target proteins
PKA = serine/threonine kinase |
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Term
| What is special about CREB and what happens to it by the catalytic subunit of PKA? |
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Definition
| PKA catalytic subunits also enter nucleus to phosphorylate (activate) transcription factors; CREB, is a TF, which binds to the CRE (cAMP responsive element) in the promoter of cAMP-responsive genes |
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Term
| What are the effects of Effects of bacterial exotoxins on signal transduction? |
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Definition
Cholera/E. coli – activate the activator
Pertussis – inhibit the inhibitor
SAME EFFECT |
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Term
| What is the result of ADP ribosylation by Cholera/E. Coli? |
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Definition
| Toxins attach ADP-ribose residue to Gαsubunit of Gs) Locks stimulatory Gsinto the active state by blocking GTPase activity |
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Term
| What is the result of ADP ribosylation by Pertussis Toxin? |
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Definition
ADP ribosylation Locks Gi into GDP-bound state; inactivates Gi
→ Prolonged & inappropriate response
SO leaves the activator ON. |
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Term
| All bacterial exotoxins do what to cytosolic cAMP? |
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Definition
| All cause ↑cytosolic cAMP & signaling, but different mechanism |
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Term
GPCRs : signalling pathway using DAG & IP3
What are the 2nd messengers? |
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Definition
1. Inositol 1,4,5- triphosphate (IP3)
2. Diacylglycerol (DAG) |
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Term
| What is IP3 and what does it do? |
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Definition
It is a 2nd messenger in the GPCR pathway
- increases Ca2+ (released from ER)*
-> Ca2+ binding proteins
-> activation PKC |
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Term
| What does Diacylglycerol (DAG) do? |
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Definition
Diacylglycerol (DAG)
activation PKC
-> activation TFs |
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Term
| What do the 2nd messengers DAG and IP3 do? |
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Definition
| DAG & IP3 activate serine/threonine kinase PKC |
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Term
| What are the two major pathways that use GPCR and G-proteins? |
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Definition
1. GPCR is associated with Gs or Gi
Effector protein= adenylcyclase
Creates cAMPas 2nd messenger
PKA is activated
2. GPCR is associated with Gq
Effector protein= phospholpase C (PLC)
Creates DAG & IP3 as 2nd messengers
PKC is activated |
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Term
| What effector proteins to activated RTKs phosphorylate? |
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Definition
PLC: IP3 and DAG (same as GPCRs)
PI3K: PKB
1. PLC
Breaks down membrane inositol phosphates to 2nd messengers;
1. IP3 -> increases Ca2+ (released from ER) -> activation PKC
2. DAG -> activation PKC -> activation TFs
2. PI3K (Phosphatidyl-inositol 3-kinase)
Phosphorylates membrane phospholipid
Products -> Activation PKB cell proliferation & growth
-> inhibition apoptosis (survival) |
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Term
| Activation of Receptor Tyrosine Kinasesreveals docking site for what proteins? |
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Definition
GRB2 binds SOS (GEF) -> activate small G-protein (Ras)
-> activates mitogen activated protein kinase (MAPK) pathway
-> TFs (Fos& Jun)
-> production GFs, GFRs, cell cycle proteins
-> cell proliferation& growth
SO basically: GRB2 binds SOS ->Ras -> MAPK |
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Term
| What is NIDDM; Non Insulin-Dependant Diabetes Mellitus? |
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Definition
RTK signalling defect
- Downregulation of insulin receptor
↓ receptor phosphorylation & TK activity
↓ 2nd messengers in pathway
→ Insulin resistance in skeletal muscle, liver, adipose tissue
(the other one is Pancreatic β-cell dysfunction → insulin deficiency
) |
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Term
| overactivation of RTKs happen what? |
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Definition
in cancers
constitutive TK activation due to increase in GF that then increase active receptors. |
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Term
| What are Cytokine receptors? CK receptors? |
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Definition
Like RTKs, but no TK
There is no intrinsic TK activity
There are proteins on these receptors (ie, JAK- tyrosine kinase).
Ligand binding activates kinase domains on proteins (JAK) that are associated with them.
STAT gene regulatory protein is activated near the CK receptor and dimerize and migrate to the nucleus.
JAK/STAT pathway |
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Term
| What does the JAK/STAT pathway do? |
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Definition
| JAK/STAT pathway (Signal Transducers & Activators of Transcription) |
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Term
| Integrin receptors are...? |
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Definition
| Receptors without tyrosine kinase activity |
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Term
| What happens when a ligand binds to integrin receptors? |
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Definition
Ligand binding→clustering of receptors which recruits &activates kinases
ILK(Integrin-linked kinase)
FAK(Focal adhesion kinase)
Can have Cooperative Integrin & RTK signalling
migration
proliferation, growth, differentiation, survival, apoptosis |
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Term
| What is similar about Intracellular receptors: Steroid Hormone Receptors? |
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Definition
They all have similar regions
-DNA binding domain and hormone binding domain. |
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