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ANSC 424 > 2 Hormone Action pt. 1 > Flashcards

2 Hormone Action pt. 1 Flashcards

1
Q

describe the process of hormone action

A

1) extracellular signals are recognized by “specific receptor” proteins
2) activated receptors start a cascade of protein activation
3) target proteins responsible for altered cell properties are turned on or off
4) cells that receive multiple signals that are integrated to determine overall response of the cell
5) target proteins may trigger a feedback circuit that shuts off the receptor or removes it from the cell surface

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2
Q

what are some examples of cell responses?

A
  • altered metabolism
  • altered gene expression
  • altered shape/movement
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3
Q

what are some examples of target proteins?

A
  • metabolic enzymes
  • gene regulatory proteins
  • cytoskeletal proteins
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4
Q

a signal is often _____ _____ during transmission and results in an on or off stage

A

exponentially amplified

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5
Q

based on location, what are the 2 classifications of receptors?

A
  • cell-surface receptors

- intracellular receptors

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6
Q

describe the structure of a cell surface receptor

A

comprised of 3 domains

  • ecto domain
  • hydrophobic transmembrane domain
  • cytoplasmic domain
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7
Q

on a cell surface receptor, where does the hormone interact?

A

NH2 of ectodomain; it has disulfide bonds and glycosylations where hormones can come and sit/interact

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8
Q

list some properties of the cell surface receptor

A
  • rich in cysteine residues (enables disulfide bridges for folding)
  • often glycosylated
  • hydrophobic transmembrane domain = alpha helix
  • domains are interchangeable
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9
Q

what are some implications of the interchangeable cell surface receptor domains?

A

you can yoink an ectodomain from one receptor and plop it on another receptor, which is beneficial for studying their functions

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10
Q

true or false: some receptors can function just as an ectodomain

A

true

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11
Q

what are free ectodomains capable of?

A

can circulate as a binding protein

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12
Q

what’s a possible cause of hyperthyroidism in Grave’s disease?

A

cleaved TSH ectodomain induces antibodies which bind to the receptor and mimic TSH action

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13
Q

what is the function of the cytoplasmic domain?

A

relays signal to the interior of the cell by inducing a signaling cascade

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14
Q

what causes conformational changes in signaling proteins?

A

activated cytoplasmic domain that:

  • phosphorylates proteins
  • binds proteins together
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15
Q

what kinds of amino acids are more prone to phosphorylation? which are more abundant?

A

hydroxylated ones

  • serine
  • threonine
  • tyrosine

serine and threonine are more abundant

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16
Q

who’s the donor of phosphate groups?

A

ATP

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17
Q

true or false: phosphorylation activates kinases

A

true, but only half true. some get deactivated by phosphorylation

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18
Q

describe signaling amplification

A

activated kinases phosphorylate other signaling proteins using ATP

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19
Q

what enzyme catalyzes phosphorylations? which catalyzes dephosphorylation?

A

kinase phosphorylates

phosphatase dephosphorylates

20
Q

when does tyrosine phosphorylation most often occur?

A

beginning of a cascade

21
Q

what function do phosphorylated tyrosines serve?

A

docking sites for downstream signal proteins

22
Q

what happens to the AA sequence that mediates docking to phosphorylated tyrosines?

A

conserved and becomes incorporated in the signaling cascade

23
Q

what types of cell surface receptors are there?

A
  • GPCRs

- Tyrosine Kinase linked

24
Q

list some of the G protein subunits

A
  • Gsa: activates adenylate cyclase
  • Gia: inhibits adenylate cyclase
  • Gqa: activates phospholipase C (IP3 and DAG and Ca signal transduction)
  • Goa: activates ion channels
  • G12/13a: regulates Actin cytoskeleton (changes shape or movement of cell)
25
Q

which class of receptor is the most numerous?

A

GPCRs

26
Q

what are GPCRs with unknown ligands called?

A

R-receptors

27
Q

how many times does the transmembrane proteins cross the lipid bilayer of a GPCR?

A

7

28
Q

true or false: GPCRs can also bind to non-endocrine ligands

A

true, e.g. glutamate (neurotransmitter), thrombin, odorants, photoreceptors

29
Q

list examples of endocrine hormone GPCRs

A

TRH, GnRH, TSH, LH, FSH, ACTH, GHRH, oxytocin

30
Q

can a hormone use more than one g-protein?

A

yes

31
Q

does location of a signal influence the activity of adenylate cyclase?

A

yes

32
Q

does hormone concentration affect g protein use?

A

yeah

33
Q

in what form do ligands come for the activation of receptors with intrinsic kinase activity?

A

a dimer

34
Q

an insulin receptor has (intrinsic/recruited) activity

A

intrinsic

35
Q

describe the structure of an insulin receptor

A

hetero-terameric structure (2 alpha and beta chains held together by disulfide bridge); 400 kDA

36
Q

which subunit of the insulin receptor is the transmembrane one?

A

beta

37
Q

what is the insulin receptor’s function?

A

associated with glucose storage

38
Q

what is the sequence of events after insulin binds to a receptor?

A

1) autophosphorylation of intracellular domain of receptor
2) docking & phosphorylation of IRS-1 and IRS-2
3) activation of 2 major pathways

39
Q

tell me about RIGRRMEK

A

insulin receptor signaling through MAPK pathway
R = receptor binds & autophosphorylates (phlts) on Tyr residues
I = IRS-1 phlted by insulin receptor on Tyr residues
G = Grb2 binds SH2 domain on the phlted Tyr of IRS-1
R = big blob of proteins binds to Ras (GTP is released)
R = activated Ras binds and activates Raf-1
M = Raf 1 phlts MEK on ser residues.
EK = MEK phlts ERK on Thr and Tyr residues, activating

ERK moves into nucleus and phlts nuclear transcription factors, activating them

40
Q

describe insulin receptor signaling through PIP3

A

1) IRS-1 phltd by insulin receptor goes and activates PI3K. PI3K converts PIP2 to PIP3
2) PKB on PIP3 is phltd by PDK1, becoming activating PKB. PKB then goes and phlts GSK3, INactivating that.
3) GSK3 can’t convert glycogen synthase to its inactive form –> GS remains active
4) synthesis of glycogen is accelerated
5) PKB stims movement of glucose transporter GLUT4 from internal vesicles to the plasma membrane, increasing uptake of glucose

41
Q

what characterizes receptors with recruited tyrosine kinase activity?

A

4 alpha-helices and homology of the ectodomain

42
Q

what are some well known recruited tyrosine kinase receptors?

A

receptors for growth hormone (HG), prolactin (PRL), and leptin

43
Q

describe the GH signaling pathway

A
  • GH has 2 binding sites; binds sequentially
  • dimerization of the cytoplasmic regions initiates signal transduction
  • recruits JAK-2
  • JAK-2 phlts itself, the receptor, and other proteins

this can then lead to 3 other branches

44
Q

what 3 branches can result from the recruitment of JAK2?

A
  • activation of transcription regulatory proteins (STAT)
  • activation of MAPK pathway
  • activation of PI3K pathway
45
Q

what does the MAPK pathway ultimately accomplish?

A

can stimulate transcription/translation of all genes needed for cell division

46
Q

what does the PIP3 pathway accomplish?

A

increased glycogen synthesis and uptake of glucose

47
Q

true or false: one cascade can effect another cascade

A

yeah, of course

ANSC 424 (12 decks)

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