Hormone Signaling Pathways Flashcards
1
Q
- Steps in hormone signaling
A
- Biosynthesis
- Storage
- Secretion
- Transport to target tissue/cell
- Recognition and binding to receptors
- Activation of signal transduction pathway (on switch)
- Amplification and relay of signal
- Cellular response
- Degredation (off switch)
2
Q
- _ and _ are the major pathways of hormones
A
- Endocrine
- Paracrine
- Note that some molecules can participate in more than one type of signaling
3
Q
- What are the two classes of hormones? What are some examples?
A
- Water soluble:
- Epi
- Insulin
- Glucagon
- GH
- Lipid soluble:
- Estrogen
- Testosterone
- Cortisol
- 1,25 Dihydroxy cholecalciferol
4
Q
- Lipophillic hormone signaling involves the _ complex acting as a transcription factor
- What are the two types of receptors?
A
- Hormone receptor complex
- Cytoplasmic receptors- bind to HRE promoter of specific genes
- Nuclear receptors- already present in nucleus bound to DNA; interactions with additional proteins activates the complex
- Both regulate transcription of specific genes
5
Q
- _ medications have short half lives (seconds to minutes)
- _ medications have long half lives (hours-days)
A
- Hydrophillic-short half lives (EX: Epi Pen)
- Hydrophobic-long half lives (EX: Birth Control)
6
Q
- What are the two cell surface receptors used for hydrophillic hormonal signaling?
A
- GPCR
- Receptor Tyrosine Kinase
7
Q
- MOA for GPCR
A
- Trimeric G protein (with alpha beta and gamma subunit) is inactive when bound to GDP
- GEF enzyme exchanges GDP for GTP
- GTP binds alpha subunit and dissociated from beta and gamma
- To become inactive, intrinsic GTPase activity, together with GAP hydrolyzes GTP to GDP, which can now bind back with beta and gamma subunits
8
Q
-
Variations in GPCR signaling:
- Gs- stimulates _
- Gi-inhibits _
- Gq- stimulates _
- Gq- activates _
A
- Gs-stimulates adenylyl cyclase, increases cAMP, PKA levels
- Gi-inhibits adenylyl cyclase, decreases cAMP and PKA
- Gt-stimulates cGMP phosphodiesterase
- Gq-Activates PLC, which increases IP3/DAG/Ca2+ levels
9
Q
- Epinephrine, via beta adrenergic receptor, activates _ and stimulates relaxation of bronchial and intestinal smooth muscle, contraction of heart, breakdown of triacylglycerols, increases breakdown of glycogen in liver and muscle, glycolysis in muscle
- Epineprhine, via alpha adrenergic receptors, activates _ protein and causes contraction of smooth muscle
A
- Gs
- Gi
10
Q
- Histamine activates _ protein on H2 receptor to cause bronchoconstriction and allergic reaction symptoms
A
- Gs
11
Q
- Dopamine activates _ protein on D2 dopamine receptor to increase HR
A
- Gi
12
Q
- ACh activates _ protein on M2 receptors to stimulate bronchoconstriction and stimulation of salivary glands
A
- Gq
13
Q
- Light via _ protein on rhodopsin induces vision
A
- Gt
14
Q
-
RTK
- What are the different domains?
- Function?
A
- Domains:
- Extracellular domain: binds ligand
- Transcellular domain
- Intracellular domain: Tyrosine kinases
- MOA:
- Binding of ligand causes dimerization
- Dimerized receptor phosphorylates tyrosine residues
- Phospho-tyrosines recognized by adaptor and docking proteins which activate RAS and RAS independent pathways
- Trigger phosphorylation of specific protein targers in cytoplasm/nucleus that alters gene transcription
- Terminated by many mechanisms (dephosphorylation, inactivation of RAS, degradation of ligand, etc)
15
Q
- Insulin is composed of an _ and _ chain
- Linked together via _ bridges
- Inactive form is stored as a _ with Zinc in the center and connected to polypeptides via _
- Active form is a _
A
- A and B
- Disulfide
- Hexamer, Histamines
- Monomer
18
Q
- Regulation of insulin secretion
A
- Glucose enters cell via GLUT 2 facilitated diffusion
- Glucokinase converts to G6P
- Synthesis of ATP
- Closing of ATP-Sensitive K+ channel
- Membrane Depolarization
- Opening of Ca2+ channels
- Release of insulin granules
19
Q
- RAS dependent insulin signaling
A
- Insulin binds RTK on muscle (already a dimer)
- Autophosphorylation of tyrosine residues
- IRS-1 phosphorylated
- IRS-1 recognized by GRB-2 initiating RAS and MAPK pathway
- Results in phosphorylation of nuclear proteins that increase transcription of glucokinase
20
Q
- RAS Independent Insulin Signaling
A
- Insulin binds RTK
- Autophosphorylation of tyrosine residues
- IRS-1 phosphorylated
- Recruits PI3 kinase
- P13 converted to PIP2 and PIP3
- PIP2 and PIP3 recruit PKB and activate its phosphorylation
- PKB stimulates:
- Movement of GLUT4 of muscle and adipose cells to their PMs
- Promotes glycogen synthesis by phosphorylating and inhibiting glycogen synthase kinase (GSK-3)
24
Q
- Molecular Structure of Nuclear Receptors and MOA
A
- Structure:
- Ligand binding domain (LBD)
- Activation Function 1 Domain (AF1)-transcription activating domain
- DNA binding domain (DBD)
- MOA:
- LBD binds molecules that regulate ligand dependent activation of receptor
- LBD undergoes conformational changes allowing recruitment and binding of co-activators or co-repressors that activate gene transcription
- DBD binds HRE (regulatory sequence on the DNA) upstream of target gene
*
25
Q
- Primary versus secondary response to steroid hormones **
A
26
Q
- Estrogen receptor= _ receptor
- _ main types
- Both are _ transcription factors
- Where are each receptor type found?
A
- Nuclear
- 2 (Alpha and Beta)
- Estrogen-dependent
- Alpha
- Uterus
- Vagina
- Ovaries
- Mammary glands
- Hypothalamus
- Endothelial Cells
- Vascular Smooth Muscle
- Beta
- Ovaries
- Prostate
- Lung
- Brian
- Bone
- Vasculature
- Many cells express both alpha and beta ERs
