2.4 Signal Transduction Flashcards
RTK acronym
receptor tyrosine kinase
Structure of an RTK
- have a ligand-binding domain
- have a transmembrane domain
- a single hydrophobic alpha helix (as opposed to GPCR that have 7 transmembrane domains)
- exist as monomers before ligan is bound
- inherent kinase activity
Ligand Binds to RTK – describe process
- ligand binds to RTK on extracellular side
- RTK monomers dimerize and phosphorylate one another
- phosphorylation of additional tyrosine residues
- SH2 of Grb2 seeks phosphorylated tyrosine of RTK and binds; Sos binds between Grb2 and inactive Ras with GDP
- Sos becomes GEF and GDP on Ras changed for GTP; Ras is now activated
- Ras activated Raf
- Raf activates MEK
- MEK activates MAPK; MAPK translocates to nucleus and activates transcription factors
common ligand examples for RTK pathway
EGF (epidermal growth factor)
what amino acid is phosphorylated in RTK?
tyrosine residues on the cytosolic side
GEF
proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosinediphosphate (GDP) to allow binding of guanosinetriphosphate (GTP)
adapter protein
accessory proteins; connecting molecules; assists in the regulation of signal
examples: Grb2 and Sos
domains of GRB2
SH3 – binds onto prolines
SH2 – seeks phosphorylated tyrosine residues
Why is Ras smaller than the alpha subunit of a Gprotein?
Ras is missing unit for GTPase activity
type of receptor often found in JAK-STAT pathways
cytokine receptors
What makes JAK unique from the the kinases we’ve studied?
no connection between the cell membrane and the kinase – purely cytoplasmic enzyme
JAK kinases are free-floating
What amino acid does JAK phosphorylate?
tyrosine
What is STAT?
a transcription factor
How does signal from ligand-binding get to JAK if JAK does not interact with the membrane?
JAK is associated with a receptor that has a ligand-binding domain – JAK itself doesn’t touch the membrane but attaches to something else touching the membrane
JAK-STAT process
- binding of ligand causing dimerization of receptors; JAK on each receptors cross-phosphorylate one another
- activated JAKS phosphorylate tyrosines on receptors
- SH2 binds phosphorylated tyrosine and has STAT with it; STAT is phosphorylated by the activated JAK
- STAT/SH2 with STAT/SH2 dimerize and dissociate from receptor – translocates to nucleus and binds to DNA
NLS
- “nuclear localization signal”
- like a signal peptide that takes a protein to the nucleus
