Serine Threonine Kinase Signaling Flashcards
What does Ras activation cumulate in?
induces a kinase cascade that cumulates in activation of MAP kinase (a serine/threonine kinase)
What can serine/threonine kinase (MAP kinase) do?
- translocate into the nucleus
- phosphorylate the OH group of many different proteins including transcription factors that regulate expression of cell cycle and differentiation specific proteins
What does kinase do?
phosphorylates a protein post-translationally
What does phosphatase do?
dephosphorylates a protein post-translationally
What supplies the phosphate for phosphorylation?
ATP
What is abnormal in hereditary hemorrhagic telangiectasia (HHT)?
TGF-beta loss of one of the alleles, so less receptors
What is the three hit hypothesis in hereditary hemorrhagic telangiectasia (HHT)?
- loss of functional allele (autosomal dominant)
- local loss of protein (shedding or somatic mutation)
- angiogenesis trigger (wound, inflammation, etc)
What are the steps of basic serine/threonine signaling?
- activation of specific smad
- (co)-Smad 4 binding
- nuclear transit
Are there variable cell responses to BMP in the receptor tyrosine kinase pathway?
yes
What are the two ligands of serine threonine kinases that result in the same pathway (with Smad4) in hereditary hemorrhagic telangiectasia?
BMP and TGF-beta
What is the influence of phosphorylation on protein activity?
- steric interference with interactions
- conformational change that alters activity
- creation of binding sites
- targeting - phosphorylation of cytoplasmic transcription factors targets Smalls and STATs to the nucleus
How is kinase activity regulated?
- inhibition of substrate binding by pseudosubstrate sequences on regulatory subunits on proteins (does not have phosphorylate-able domain)
- phosphorylation of activation loops turns on tyrosine kinases and activates many serine tyrosine kinases
- phosphorylation inhibits some kinases
How does phosphorylation target sites of activity?
- triggers nuclear localization of MAPK, Smads, and STATs
- kinase anchoring proteins (AKAPs) target protein kinase A (PKA) to microtubules, ER, plasma membrane, and centrosomes
What are adapter protein domains?
small independently folded domains that link proteins together in assemblies that organize functional signal transfusing machines (on many signaling proteins)
What happens when receptor serine tyrosine kinases are activated?
- ligand binding brings together pairs of type I and type II receptors
- turns on the activity of type I receptors
