Hormone Signaling Pathways Flashcards
(37 cards)
Activation of hormones involves binding to a ____ on cells and activating _______ and/or alteration in gene expression that lead to a response.
Receptor
Signal transduction
Nine steps of hormone signaling
Biosynthesis Storage Secretion Transport to target tissue/cells Recognition and binding to receptors Activation of signal transduction Amplification and relay of signal Cellular response Degradation
Stimulus -> hormone released from signaling cell -> signaling molecules travel to their target cell (through blood, etc.) -> ____ signals can easily enter membrane of target cell (can use a receptor) -> begins a cellular response
Hydrophobic
Signaling molecule released by a cell distant from target cell and transported via bloodstream to target cell
Endocrine signaling
Ex: epinephrine
Signaling molecule released by one cell type and diffuses to a neighboring target cell (locally) of a different cell type
Paracrine signaling
Ex: testosterone
Signaling molecule acts on the same cell type as the secreting cell
Autocrine signaling
Ex: Interleukin 1
Signaling molecule stays attached to the secreting cell and binds to a receptor on an adjacent target cell (forms bridge)
Juxtacrine signaling
Ex: heparin
What are hydrophilic hormones?
Do they use a second messenger?
Examples?
Receptors?
Can not penetrate the plasma membrane so interact with specific receptors at the cell surface
Yes, the receptor complex initiates production of a second messenger inside the cell that triggers a cellular response (cAMP, Ca, IP3)
NE, E, insulin, glucagon, histamine, serotonin, melatonin, dopamine, ACh, cytokines, TSH
G protein-coupled receptors, receptor tyrosine kinases
What are lipophilic hormones?
Do they use a second messenger?
Examples?
Receptors?
Pass through plasma membrane
No, the hormone binds to specific receptor proteins inside the cell; molecule receptor complex acts as a transcription factor
Progesterone, estradiol, testosterone, cortisol, aldosterone, vitamin D, thyroxine, retinol, retinoic acid
Cytoplasmic receptors, nuclear receptors
_____ receptors exist in an inactive complex with the HSP 90; HSP dissociates; the hormone-receptor complex translocates to the nucleus where it binds to a DNA sequence called ______ in the promoter region of specific genes.
Cytoplasmic receptors
Hormone response element (HRE)
This receptor is already present in the nucleus and bound to DNA; the hormone signal activates the complex.
Nuclear receptor
Hydrophilic medications have a ____ half life.
Example?
Lipophilic medications have a _____ half life.
Example?
Short
Epinephrine; used to treat severe acute allergic rx
Long
Oral contraceptives
How are G protein coupled receptors activated and inactivated? (GPCR)
What role do GEF and GAP play?
G protein with three subunits
Inactive G protein exchanges GDP for GTP through the action of the guanine nucleotide exchange factor (GEF)
Active GTP alpha subunit separates from beta and gamma to do the work
To return to inactive, intrinsic GTPase activity of G protein hydrolyzes GTP to GDP and Pi; accelerated by GTPase-activating protein (GAP)
Fx GPCR signaling variations:
Gs?
Gi?
Gt?
Gq?
Stimulates adenylate cyclase, forms cAMP, PKA, phosphorylates targets (epinephrine with beta adrenergic receptor, histamine)
Inhibits adenylate cyclase (E and NE with alpha receptor, dopamine)
Stimulates hydrolysis of cGMP by phosphodiesterase
Works through phospholipase C, IP3, activation of PKC (ACh)
What is receptor tyrosine kinase? (RTK)
How does it work?
How is it terminated?
Extracellular domain that binds to a ligand
RTK binds to a ligand (hydrophilic hormone) causing dimerization; dimerized receptor then phosphorylates tyrosine residues; phosphotyrosines are recognized by adaptor and docking proteins; this activates downstream signaling pathways (RAS dependent/independent); this triggers phosphorylation of specific protein targets that alter gene expression
Degradation of ligand, RAS inactivation, dephosphorylation, ligand-induced endocytosis of receptor
Insulin synthesis and secretion:
____ upregulates preproinsulin mRNA
Translated into ____ and translocated to ____ lumen
Cleaved by ____ to form proinsulin
Folded and transported to _____.
Packaged into immature ______ then cleaved by ____ to form insulin and C peptide
Immature granules become _____ that contain hermetic crystalized _____.
____ and ____ are released together.
Glucose
Preproinsulin; ER
Protease
Golgi
Granules; proteases
Mature granules; insulin
Insulin and C peptide
____ stimulates the release of insulin in two phases, what are they?
Where does each release get their insulin granules?
Glucose
First and second
First: limited pool of granules called readily releasable pool (RRP)
Second: larger pool called reserve pool
Glucose in blood -> enters pancreatic ___ cells though ___ transporter -> glucokinase phosphorylates glucose -> glycolysis -> TCA cycle -> make ATP -> ___ levels of ATP close K+ channel -> causes ____ of membrane -> opens Ca channel -> helps release insulin granules from pancreatic beta cells
Beta
GLUT 2
High
Depolarization
What type of signaling does insulin use?
Receptor tyrosine kinase
Describe insulin signaling through the RAS-dependent RTK pathway
Insulin binds to dimerized insulin receptor -> phosphorylation of insulin receptor -> recruits insulin receptor substrate (IRS-1) -> IRS-1 is phosphorylated and binds to adaptor protein GRB-2 -> activates RAS and MAPK pathway -> phosphorylation of proteins -> alters gene expression of glucokinase -> stimulate glycolysis and glycogen synthesis -> lowers blood sugar
Describe insulin signaling through the RAS-independent RTK pathway
Insulin binds to dimerized insulin receptor -> phosphorylation of insulin receptor -> recruits insulin receptor substrate (IRS-1) -> IRS-1 is phosphorylated and recruits enzyme PI3-kinase -> activates PKB -> phosphorylates proteins causing translocation of GLUT 4 (transporter in muscle and adipocytes) -> GLUT 4 moves from cytoplasm to plasma membrane -> influx of glucose and increase glycogen synthesis
Reduced sensitivity to insulin (normal amount of insulin doesn’t cause the expected response)
Insulin resistance
What causes insulin resistance?
Defects in insulin signaling (receptor activation to translocation of GLUT 4 transporters in adipose and muscle tissue)
Mutations in insulin receptor
Defect in insulin binding domain on extracellular side
Variations in intracellular domain
Insulin resistance can be caused from increased phosphorylation of a ____ domain by ____ kinase instead of tyrosine in the insulin receptor.
This inhibits formation of ____ which prevents both RAS pathways.
____ kinase is activated by cytokines, free fatty acids, DAG, ceramide, inflammatory molecules.
Serine
Ser/Thr kinase
IRS
Ser/Thr kinase
