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Bs 3054 - molecular and cellular Pharmacology > Topic 3: Signal transductions > Flashcards

Topic 3: Signal transductions Flashcards

1
Q

What does differential regulation (regulated by multiple molecules) allow a cell to do?

A

it allows for cell specific responses to extra cellular signals (depends on what AC iosforms are present)
there is cross talk with other signalling pathways

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2
Q

what effctors can cAMP mediate

A

Cyclic nucleiotde gated channels
cyclic nucelotide regulated GEFs
cAMP-dependent protein kinase A - PKA

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3
Q

What do protein kinases do?

A

Phasperalte proteins that have a specific consensus recognition sequence.

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4
Q

How many cAMP binding sites are on the PKA holoenzyme

A

4 on the regulatory subunit dimer.

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5
Q

how many isofroms are there of the regulatory subunit of PKA holoenzyme

A

4
R1a, R1B and R2a and R2B

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6
Q

how many catylic PKA isoforms are there?

A

3
Ca CB CY

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7
Q

are the regulatory subunits for PKA homo or hetromultimers?

A

both

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8
Q

what is the mechism of action for activation of PKA?

A

PKA exists in an inactive holoenzyme
4 cAMP binds to the regulatory dimer, reguatory and catalytic subunits dissociate
catalytic subunit is now active

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9
Q

what is an AKAP? what class of PKA enzymes are they associated with?

A

A-kinase anchoring protein - binds PKA II to cellular targets

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10
Q

What are the two main classes of PKA

A

PKA I
PKA II

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11
Q

What is an EPAC?

A

Exchange protein directly activated by cAMP
Functions as a GEF for the Ras like gtpases Rap1 and Rap2

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12
Q

What is a phosphodiesterase?

A

Proteins that hydrolyse cyclic nucleotides.
three main types
cGMP and cAMP selective
cAMP preference
cGMP preference

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13
Q

How do we achieve cAMP microdomains

A

AKAPs - bind to R subunits of PKA can have subcellular localisation
Caveolae - (little caves in membranes) activities regulated by signalling proteins present or by calveolin.
Localisation of Phosphodiesterises - limits sphere of influence of cAMP.
isoforms if AC and PDE each differentially regulated by proteins found in that particular sub compartment.

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14
Q

what is a particulate guanylyl cyclase?

A

A enzyme homodimeric that produces cGMP , is membrane bound and is activated by ligands

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15
Q

what are cytosolic GC

A

a GC that is activtated by NO and CO as it cointians a heme group

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16
Q

how long does NO last in the body

A

seconds, made as an when needed. also readly diffuses into surrounding cells

17
Q

how is NO synthesises

A

By NOS which is controlled by Ca2+

18
Q

What can cGMP effect

A

PKG, modulation of phosphodiesterase activity and cyclic nucleotide gated channels.

19
Q

What class of molecules do phospholipases act on?

A

they act on gycerophospholipids

20
Q

what does phospholipase produce from PIP2

A

DAG and IP3

21
Q

how many isoforms of PLC is there? why is this important

A

13, it allows for a large number of persise control

22
Q

what molecules can IP3 stimulate

A

inositol phopatases multiple kinases transcription and RNA processing

23
Q

what molecules can DAG stimulate

A

enzyumes and structural proteins with C1 domin eg PKC
phosphatidic acid.

24
Q

what do phosphatidylinositol 3- kinases phosphorylate?

A

the 3 prime position of the innosital ring in phosphatidylinositol

25
Q

what activates PI3Ks?

A

cell surface receptors particularly those with intrinsic tyrosine kinase activity eg RTK

26
Q

what is PI3Ks preferred substrate invivo ?

A

PtdIns(4,5)P2 (PIP2)

27
Q

what is the mechism of activation of Class 1a PI3Ks check

A

has alot of SH2 domoins so activated RTK will allivated inhibiation by regutory subunit (P85) and bring catalytic subunit close to PIP2 to make PIP3

28
Q

What does PIP3 act on

A

Acts as a anchor for various signalling proteins with PH (pleckstrin-homology) that accumulate at sites of PI3K activation by binding to PIP3 such as
Rho GTPases
PLCy
PKB

29
Q

how is PIP3 signalling terminated?

A

SHIP - removes binding site for PH domain but generates PtdIns(3,4)P2 which can bind to PKB (PKB binds PtdIns(3,4)P2 and PtdIns(3,4,5)P2 with the same affinity) .
PTEN removes both PtdIns(3,4,5)P2 and PtdIns(3,4)P2 and so inhibits PKB

Bs 3054 - molecular and cellular Pharmacology (7 decks)

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