Flashcards in Actions of hormones - cell signalling Deck (21)
how do hormones target specific cell types?
Only the target cells for a particular hormone express receptors for binding with this hormone
what is signal transduction?:
Process where incoming signals are conveyed into the target cell where they are transformed into the dictated cellular response
Describe how hydrophilic hormones alter pre-existing proteins via second messenger systems.
Most hydrophilic hormones bind to G-protein-coupled receptors (GPCRs)
Target cell effects of hormone binding are mediated via second-messenger systems (hormone is first messenger)
what are the two major second-messenger pathways?
-Cyclic adenosine monophosphate (cAMP)
what do both pathways have in common?
Both pathways use a G protein (inner surface of PM) which acts as an intermediary between the receptor and an effector protein
what is the active and inactive state of G proteins?
Guanosine triphosphate (GTP) when active, or
Guanosine diphosphate (GDP) when inactive
what does an inactive G protein consist of?
3 subunits: alpha, beta and gamma
GDP is bound to the alpha subunit
Describe the signal transduction with GPCRs.
-Hormone (1st messenger) binds to cell surface receptor
-Receptor attaches to G protein, resulting in release of GDP from the G protein complex.
-GTP then attaches to the alpha subunit, which activates the G protein.
-The alpha subunit dissociates from beta and gamma subunits and moves along the inner surface of the PM until it reaches an effector protein (enzyme or ion channel).
-The alpha subunit links up with the effector protein and alters its activity
what are the two major G-protein coupled effectors?
1) Adenylyl cyclase (cAMP)
2) Phospholipase C (Ca2+)
what does adenylyl cyclase do?
converts (intracellular) ATP to cAMP
what does cAMP do?
activates a specific intracellular enzyme Protein Kinase A (PKA)
what does PKA do?
phosphorylate a pre-existing intracellular protein (Thr residues e.g. a metabolic enzyme)
why can cAMP induce differing responses in different cells?
Different cell types express different proteins that are phosphorylated by PKA
what is the effect of glucagon ?
breakdown & reduced
Describe the actions of phospholipase C & Ca2+.
-Binding of the hormone, via G-protein, activates an enzyme Phospholipase C (PLC; inner side of PM)
-PLC breaks down PIP2 (phosphatidylinositol bisphosphate) to yield DAG (diacylglycerol) and IP3 (inositol trisphosphate)
-DAG remains in the lipid bilayer of PM, IP3 diffuses into the cytosol
-IP3 stimulates release of Ca2+ from the ER
-Ca2+ can influence the activity of ion channels, enzymes, secretion of other hormones etc. to produce a biological response.
-DAG regulates Protein Kinase C -(PKC) activity
PKC phosphorylates (Ser residues on) specific intracellular proteins.
Phosphorylated intracellular proteins accomplish the biological response to hormone binding
Describe why amplification is important.
Low concentration of primary messenger- trigger more pronounced cellular response
what peptide hormone does not act via a G-protein-coupled receptor?
what does insulin bind to?
insulin binds to its cell surface receptor and activates ‘autophosphorylation
what is an insulin receptor an example of?
Describe how lipophilic hormones promote synthesis of new proteins.
-Steroid hormones, calcitriol and thyroid hormone can all cross the cell membrane and bind to intracellular receptors (cytoplasmic or nuclear).
-Each receptor has a hormone binding region and a DNA binding region.
-The hormone-receptor complex binds with DNA at a specific attachment site: hormone response element (HRE)
-DNA transcription of specific genes can be induced (or suppressed)
-Result: changes in cellular expression of proteins encoded by these genes