2 Hormone Action pt. 1 Flashcards
describe the process of hormone action
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
what are some examples of cell responses?
- altered metabolism
- altered gene expression
- altered shape/movement
what are some examples of target proteins?
- metabolic enzymes
- gene regulatory proteins
- cytoskeletal proteins
a signal is often _____ _____ during transmission and results in an on or off stage
exponentially amplified
based on location, what are the 2 classifications of receptors?
- cell-surface receptors
- intracellular receptors
describe the structure of a cell surface receptor
comprised of 3 domains
- ecto domain
- hydrophobic transmembrane domain
- cytoplasmic domain
on a cell surface receptor, where does the hormone interact?
NH2 of ectodomain; it has disulfide bonds and glycosylations where hormones can come and sit/interact
list some properties of the cell surface receptor
- rich in cysteine residues (enables disulfide bridges for folding)
- often glycosylated
- hydrophobic transmembrane domain = alpha helix
- domains are interchangeable
what are some implications of the interchangeable cell surface receptor domains?
you can yoink an ectodomain from one receptor and plop it on another receptor, which is beneficial for studying their functions
true or false: some receptors can function just as an ectodomain
true
what are free ectodomains capable of?
can circulate as a binding protein
what’s a possible cause of hyperthyroidism in Grave’s disease?
cleaved TSH ectodomain induces antibodies which bind to the receptor and mimic TSH action
what is the function of the cytoplasmic domain?
relays signal to the interior of the cell by inducing a signaling cascade
what causes conformational changes in signaling proteins?
activated cytoplasmic domain that:
- phosphorylates proteins
- binds proteins together
what kinds of amino acids are more prone to phosphorylation? which are more abundant?
hydroxylated ones
- serine
- threonine
- tyrosine
serine and threonine are more abundant
who’s the donor of phosphate groups?
ATP
true or false: phosphorylation activates kinases
true, but only half true. some get deactivated by phosphorylation
describe signaling amplification
activated kinases phosphorylate other signaling proteins using ATP
what enzyme catalyzes phosphorylations? which catalyzes dephosphorylation?
kinase phosphorylates
phosphatase dephosphorylates
when does tyrosine phosphorylation most often occur?
beginning of a cascade
what function do phosphorylated tyrosines serve?
docking sites for downstream signal proteins
what happens to the AA sequence that mediates docking to phosphorylated tyrosines?
conserved and becomes incorporated in the signaling cascade
what types of cell surface receptors are there?
- GPCRs
- Tyrosine Kinase linked
list some of the G protein subunits
- 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)
which class of receptor is the most numerous?
GPCRs
what are GPCRs with unknown ligands called?
R-receptors
how many times does the transmembrane proteins cross the lipid bilayer of a GPCR?
7
true or false: GPCRs can also bind to non-endocrine ligands
true, e.g. glutamate (neurotransmitter), thrombin, odorants, photoreceptors
list examples of endocrine hormone GPCRs
TRH, GnRH, TSH, LH, FSH, ACTH, GHRH, oxytocin
can a hormone use more than one g-protein?
yes
does location of a signal influence the activity of adenylate cyclase?
yes
does hormone concentration affect g protein use?
yeah
in what form do ligands come for the activation of receptors with intrinsic kinase activity?
a dimer
an insulin receptor has (intrinsic/recruited) activity
intrinsic
describe the structure of an insulin receptor
hetero-terameric structure (2 alpha and beta chains held together by disulfide bridge); 400 kDA
which subunit of the insulin receptor is the transmembrane one?
beta
what is the insulin receptor’s function?
associated with glucose storage
what is the sequence of events after insulin binds to a receptor?
1) autophosphorylation of intracellular domain of receptor
2) docking & phosphorylation of IRS-1 and IRS-2
3) activation of 2 major pathways
tell me about RIGRRMEK
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
describe insulin receptor signaling through PIP3
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
what characterizes receptors with recruited tyrosine kinase activity?
4 alpha-helices and homology of the ectodomain
what are some well known recruited tyrosine kinase receptors?
receptors for growth hormone (HG), prolactin (PRL), and leptin
describe the GH signaling pathway
- 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
what 3 branches can result from the recruitment of JAK2?
- activation of transcription regulatory proteins (STAT)
- activation of MAPK pathway
- activation of PI3K pathway
what does the MAPK pathway ultimately accomplish?
can stimulate transcription/translation of all genes needed for cell division
what does the PIP3 pathway accomplish?
increased glycogen synthesis and uptake of glucose
true or false: one cascade can effect another cascade
yeah, of course
