Hormone action Flashcards
steps in GPCR singling through IP3 and Ca (7)
- hormone binds to specific receptor
- occupied receptor causes GDP to be replaced by GTP on Gq-alpha
- Gq-alphae bound to GTP moves to phospholipase C (PLC) and activates it [membrane bound]
- activated PLC cleaves PIP2 into IP3 (inositol triphosphate) and diacylglycerol (DAG)
- IP3 binds to a specific receptor-gated calcium channel, releasing sequestered calcium
- DAG and Ca activate protein kinase C at the surface of the plasma membrane
- phosphorylation of cellular proteins by PKC produces some of the cellular responses to the hormone
what are the 2 products of PIP2 cleavage?
IP3 and DAG
what molecule cleaves PIP2?
PLC
which G-alpha subunit activates PLC?
Gq-alpha
where is DAG located?
membrane bound
where is IP3 found?
free in cytoplasm
hormones may use more than one G-protein. true or false?
true
why is singling through GPCR complex?
use can change during development and use can change depending on hormone concentration or in different tissues
what are the two types of receptors involved with tyrosine kinase?
- receptors with an integrated (intrinsic) kinase activity
2. receptors that recruit a kinase
what is a tyrosine kinase?
kinase that specifically phosphorylates tyrosine residue on a protein
which are the most studied RTK?
insulin receptor and IGF-1 receptor
which type of RTK are the insulin receptors and IGF-1 receptors?
receptors with intrinsic tyrosine kinase activity
what is the structure of the insulin receptor?
hetero-tetrameric structure 2 alpha and 2 beta chains held together by disulphide bonds
=> 2 types of subunits, 4 subunits in total
how is the insulin receptor synthesized?
from a single precursor protein
where are insulin receptors most abundant?
adipocytes and hepatocytes
what is the series of events after insulin binding? (3)
- autophosphorylation (intrinsic kinase activity) of intracellular domain of receptor (carboxylic end)
- docking and phosphorylation of IRS-1 or IRS-2 (insulin receptor substrate)
- activation of 2 major signal pathways MAPK and PIP3
which signaling pathways does insulin binding trigger?
MAPK and PIP3
steps involved in Insulin receptor signaling through MAPK pathway (7)
- insulin receptor binds insulin and undergoes autophosphorylation on its carboxyl-terminal Tyr residues
- insulin receptor phosphorylates IRS-1 on its tyrosine residue
- SH2 domain of Grb2 binds to phosphorylated-Tyr of IRS-1, Sos binds to Grb2, then to Ras, causing GDP release and GTP binding to Ras
- activated Ras binds and activates Raf-1
- Raf-1 phosphorylates MEK on two Ser residues, activating it. MEK phosphorylates ERK on a Thr and a Tyr residue, activating it
- ERK moves into the nucleus and phosphorylates nuclear transcription factors such as Elk1, activating them
- phosphorylated Elk1 joins SRF to stimulate the transcription and translation of a set of genes needed for cell division