Part 2 Flashcards
(10 cards)
What are the main steps leading up the hormonal activation of adenylyl cyclase by the hormone epinephrine?
Hormone binds to extracellular domain of receptor. Binding of hormone causes a conformational change in the intra cellular domain which activates the G protein associated with it. G protein dissociates from the receptor and carries signal to intracellular target.
What role do ‘GTPase activating proteins’ (GAP) have in regulating G protein signaling?
Normally G proteins are regulated by GAP which results in controlled cell division. Without GAP proteins constitutively, they are unregulated cell division and formation of tumors.
What are the main steps leading to regulation of glycogen breakdown?
1) Epinephrine stimulates adenyl cyclase to synthesize cAMP
2)Most effects of cAMP are mediated by the action of cAMP dependent kinases or PKA
3) PKA is a tetramer consisting of two regulatory subunits and two catalytic subunits (inactive state)
4) cAMP binds to regulatory subunits
5) Binding of cAMP to the regulatory subunits induces conformational change and causes dissociation of the catalytic subunits
6) Catalytic subunits now enzymatically active phosphorylate serine residues in target proteins
7) Catalytic subunits phosphorylate phosphorylase kinase which in turn phosphorylates glycogen phosphorylase
8) Glycogen phosphorylase then catalyzes the breakdown of glycogen to glucose
How does cholera toxin negatively impact the normal signaling pathway for adenylyl cyclase activation specifically, what is the mechanism of action for cholera toxin?
Chlorea toxin inhibit the ability of the alpha subunits of Gs to hydrolyze GTP
How is protein kinase A regulated (activated/inactivated)?
cAMP activates kinase with 2 regulatory and 2 catalytic subunits. Binding of cAMP to regulatory subunits induces conformational change that dissociation on catalytic subunits then they are active - activates PKA
What are the main steps that lead to expression of cAMP-inducible genes?
1) Receptor stimulation leads to G protein activation of adenyl cyclic synthesis of cAMP and activation of PKA
2) Free catalytic subunit of PKA translocate to the nucleus and phosphorylates the Transcription factor
3) Leads to recruitment of coactivators and expression of cAMP inducible genes
Compare the differences between receptor tyrosine kinases and non-receptor tyrosine kinases?
RTK = Transmembrane proteins - phosphorylate themselves and downstream targets upon ligand binding- initiates signaling directly at cell membrane
NRTK = Lack a transmembrane domain and rely on sperate receptors for signaling proteins for activation. Function in various intracellular pathways.
What are the main steps that lead to activation of receptor tyrosine kinases?
N terminal extra cell ligand bindind domain single transmembrane alpha helix with tyrosine kinase activity
1. Growth factor binding induces receptor dimerization
2. The 2 pp chains cross phosphorylate one another.
What is the role of Ras in ERK MAP kinase signaling (specifically how is Ras regulated)?
Ras alternates between inactive GDP and active GTP-bound states. Required for response of cells to growth factor stimulation = Ra activation, GEF termination and GAP stimulate GTP hydrolysis.
Under what circumstances would Ras be directly responsible for causing abnormal cell growth?
Ras is directly responsible for causing abnormal cell growth. When there is a mutation of Ras genes that inhibit GTP hydrolysis by the Ras proteins. Means always active = causing cell growth.
