Endocrine Receptors and Signaling Pathways DSA

Question 1

Hormones- 5 classes

Answer 1

• aa derivatives- dopamine, catecholamines, TH
• small neuropeptides- GnRH, TRH, somatostatin, vasopressin
• large proteins- insulin, LLH, PTH
• steroid Hs- cortisol, estrogen
• vitamin derivatives- retinoids (vit A), Vit D

Question 2

what H’s interact with cell-surface membrane R’s?

Answer 2

• aa derivatives

- peptide H’s

Question 3

what H’s interact with intracellular nuclear R’s?

Answer 3

• steroids
• TH
• vit D
• retinoids

Question 4

4 types of R’s

Answer 4

• ligand-gated ion channels
• GPCRs
• kinase-linked Rs
• nuclear Rs

Question 5

GCPRs- B-adrenergic, LH, FSH, TSH, glucagon, PTH, PTHrP, ACTH, GHRH, CRH- effectors, signaling pathways

Answer 5

• Galphas»»>Ca channels

- stim of cAMP»»>calmodulin, Ca-dep kinases

Question 6

GPCRs- alpha-adrenergic, somatostatin- effectors, signaling pathways

Answer 6

• Galphai

- inhibition of caMP prod; act of K, Ca channels

Question 7

GPCRs- TRH, GnRH- effectors, signaling pathways

Answer 7

• Galphaq, Galpha11

- PLC, DAG, IP3, PKC, voltage-gated Ca channels

Question 8

R tyrosine kinase- insulin- effectors, signaling pathways

Answer 8

• tyrosine kinases, IRS-1 to IRS-4

- MAP kinases, Pl 3-kinase, RSK

Question 9

Cytokine R-linked kinase- GH, PRL- effectors, signaling pathways

Answer 9

• JAK, tyrosine kinases

- STAT, MAP kinase, Pl 3-kinase, IRS-1 and 2

Question 10

Serine kinase- TGF-B- effectors, signaling pathways

Answer 10

• serine kinase

- smads

Question 11

Kinase-linked R’s- main types

Answer 11

• RTKs (insulin R)
• serine/threonine kinase R’s (TGF-B)
• cytokine R’s- lack intrinsic enzyme activity (Rs for GH and PRL)

Question 12

kinase signaling cascade mechanisms

Answer 12

• ligand binding to kinase-linked R
• R dimerization
• autophosphorylation of intracellular tyrosine residues- high affinity binding sites for intracellular proteins
• act or inhibit (via phosphorylation) TFs

Question 13

G-proteins- 3 subunits

Answer 13

• alpha- binds to guanine nucleotides, act effector proteins when bount to GTP, has enzymatic activity
• By dimer- membrane localization of the G-protein and directs signaling

Question 14

G-protein- activation- what happens

Answer 14

• resting state- G-protein exists as an unattached GalphaBy trimer assoc with the cytoplasmic side of the membrane
• when act by a hormone agonist- acquires high affinity for the GalphaBy
• bound GDP dissociates- replaced with GTP
• releases Galpha-GTP and GBy subunits
• GTPase activity of alpha-subunit- signal terminated

Question 15

targets for G-proteins

Answer 15

• AC- inc cAMP prod
• PLC- IP3 and DAG formation
• ion channels- Ca and K
• Rho A/Rho kinase

Question 16

AC system

Answer 16

• in caMP prod
• cAMP act protein kinase A
• cAMP inact by PDE

Question 17

PLC system

Answer 17

• PLC act by Galphaq
• PIP2 splits into DAG and IP3
• IP3- binds to R- ligand-gated Ca channel on memb of ER- Ca released from intracellular stores
• DAG (lipophilic remains in membrane)- act PKC- phosphorylates proteins

Question 18

ion channels as targets for G-proteins

Answer 18

-By subunit interacts with the channel!

Question 19

Rho system

Answer 19

• member of the Rho family of GTPases
• act supported by GEFs (promote the exchange of GDP for GTP)
• inact by GAPs (promote hydrolysis of GTP to GDP)
• Rho-GTP act Rho kinase- phosphorylates proteins

Question 20

Nuclear R’s- 3 main domains

Answer 20

• AF1 (activation function)
• DBD (DNA binding domain)- binds to specific DNA sequences (HREs) upstream of the target gene
• LBD (ligand-binding domain)- confers ligand-dep act

Question 21

classification of Nuclear R’s

Answer 21

• classic steroid nuclear Rs (GR, MR, ER, PR, AR)

- orphan Rs (ligands are unknown)

Question 22

Nuclear R’s- heterodimerization vs homodimerization

Answer 22

• some nuclear Rs bind to the HREs after ligand binding and act transcription only after homodimerization with the same type of R (glucocorticoid, androgen, progesterone, estrogen Rs)
• others only after heterodimerization with a diff type of R
• heterodimers- RXR and RAR