ESR. 005. Hydrophilic hormones and and enzymes cascades Flashcards

1
Q

what causes the activation of the G-alpha subunit in a GPCR

A

hormone bound to receptor cuases exchange of GDP to GTP

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2
Q

what is the structure of a GPCR

A

7 alpha helices which span the membrane

the G protein part in heterotrimeric

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3
Q

what are the 4 types of G alpha subunit

A

Gs- activates adenyl cyclase - increasing cAMP
Gi - inhibits adenyl cyclase -reducing cAMP
Gq - activates phospholipase C - increasing DAG, IP3 AND Ca2+
Gt - activates cyclic GMP phosphodiesterase

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4
Q

what type of Ga does the beta adrenergic receptor activate

A

Gs

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5
Q

what does cAMP do at the beta adrenergic receptor

A

causes the removal of the regulatory protein off the PKA

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6
Q

how does GTP cause a conformational change in the heterotrimeric G protein

A

the phosphate on the GTP - has a negative charge and slightly changes the shape of the protein
the switch 2 alpha helix is free now to interact and activate adenyl cyclase

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7
Q

how is the V. cholera toxin harmful on intestinal epithelial cell?

A

covalently modifies the alpha subunit so it is permanently activated
this works on the Gs so causes lots of adenyl cyclase and so lots of cAMP made

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8
Q

how does the B pertussis toxin affect the cell?

A

causes AD ribosylation of the Gi subunit - preventing it from interacting with the GPCR - it cannot be activated and therefore have inhibition of the inhibition and loads of cAMP made

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9
Q

what is the structure of protein kinase A

A

R2C2 hetertetramer

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10
Q

which two amino acids is PKA for

A

serine and threonine

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11
Q

what is the consensus sequence that PKA recognises

A

Arg.Arg. X. Ser/Thr. Z

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12
Q

how many cAMPs need to bind to regulatory subunits to make them dissociate from PKA

A

4

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13
Q

what type of enzyme is tyrosine kinase

A

receptor enzyme - extracellular ligand binding domain, enzyme active site in intracellular region connected by a single transmembrane segment
eg. insulin receptor

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14
Q

which receptor does epidermal growth factor attach to?

A

tyrosine kinase

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15
Q

what happens to the receptor after the hormone binds

A

causes the monomer to expose an interaction site for a homologous recepor
- they can phosphorylate each other

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16
Q

after cross-phorylation which protein binds to the homodimer

A

Grb-2

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17
Q

what is the important domain on Grb -2 and which protein binds to it

A

SH2 domain

Sos protein attaches to Grb-2

18
Q

where is Ras found

A

membrane bound

- it is a monomeric G protein

19
Q

to which protein does Ras bind

A

Sos (after is has been picked up from cytosol by Grb-2)

20
Q

what action activates Ras?

A

exchange of GDP for GTP ( mediated by Sos once recruited by Grb-2)

21
Q

what protein does activated RAs bind to

A

Raf (also membrane bound)

22
Q

is tyrosine kinase active in it monomeric form?

A

yes

- although its not close enough to another monomer to cross-phosphorylate

23
Q

what receptor is overexpressed in epithelial cancers?

A

EGFR

24
Q

what is the name of the antibody that blocks EGFR

A

cetuximab

- prevents dimerisation

25
Q

in what cancer is cetiximab successful?

A

colorectal cancer

26
Q

in the insulin receptor a monomer or dimer?

A

dimer

27
Q

once the insulin dimer has cross-phosphorylate what is the next protein that binds to it

A

IRS-1 (membrane bound)

28
Q

once IRS-1 has been phosphorylated what protein binds to it

A

PI-3K - in the cytosol

29
Q

what is the function of TGFbeta

A

prevents proliferation of most mammalian cells by inducing synthesis of proteins that inhibit the cell cycle

30
Q

what type of hormone is TGFbeta

A

autocrine

31
Q

name a protein used to strengthen bone fractures

A

BMP7

32
Q

to what monomer does TGFbeta first bind

A

TRB-II

33
Q

TRB-II then binds to TRB-I - what happens next?

A

its glycine - serine rich (GS) domain is phosphorykated - activating the S/T kinase activty

34
Q

what transcriptions factors does TRB-I phosphorylate

A

R-smads

35
Q

what heterotrimer forms upon phosphorylation

A

two-Rsmads and a co-smad

- nuclear localisation signals exposed

36
Q

what element of the TGFbeta pathway is lost in most human pancreatic cancers

A

Smad4 - a co-smad

37
Q

what enzyme is bound to the cytosolic domain of cytokine receptors?

A

the tyrosine kinase JAK

38
Q

what do JAKs phosphorylate?

A

STATs

39
Q

how many receptors can EPO bind to

A

two cytokine receptors - bringing them together

40
Q

what inhibits the JAK/STAT pathway

A

SHP1