2.4 Signal Transduction

Question 1

RTK acronym

Answer 1

receptor tyrosine kinase

Question 2

Structure of an RTK

Answer 2

• 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

Question 3

Ligand Binds to RTK – describe process

Answer 3

1. ligand binds to RTK on extracellular side
2. RTK monomers dimerize and phosphorylate one another
3. phosphorylation of additional tyrosine residues
4. SH2 of Grb2 seeks phosphorylated tyrosine of RTK and binds; Sos binds between Grb2 and inactive Ras with GDP
5. Sos becomes GEF and GDP on Ras changed for GTP; Ras is now activated
6. Ras activated Raf
7. Raf activates MEK
8. MEK activates MAPK; MAPK translocates to nucleus and activates transcription factors

Question 4

common ligand examples for RTK pathway

Answer 4

EGF (epidermal growth factor)

Question 5

what amino acid is phosphorylated in RTK?

Answer 5

tyrosine residues on the cytosolic side

Question 6

GEF

Answer 6

proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosinediphosphate (GDP) to allow binding of guanosinetriphosphate (GTP)

Question 7

adapter protein

Answer 7

accessory proteins; connecting molecules; assists in the regulation of signal

examples: Grb2 and Sos

Question 8

domains of GRB2

Answer 8

SH3 – binds onto prolines

SH2 – seeks phosphorylated tyrosine residues

Question 9

Why is Ras smaller than the alpha subunit of a Gprotein?

Answer 9

Ras is missing unit for GTPase activity

Question 10

type of receptor often found in JAK-STAT pathways

Answer 10

cytokine receptors

Question 11

What makes JAK unique from the the kinases we’ve studied?

Answer 11

no connection between the cell membrane and the kinase – purely cytoplasmic enzyme
JAK kinases are free-floating

Question 12

What amino acid does JAK phosphorylate?

Answer 12

tyrosine

Question 13

What is STAT?

Answer 13

a transcription factor

Question 14

How does signal from ligand-binding get to JAK if JAK does not interact with the membrane?

Answer 14

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

Question 15

JAK-STAT process

Answer 15

1. binding of ligand causing dimerization of receptors; JAK on each receptors cross-phosphorylate one another
2. activated JAKS phosphorylate tyrosines on receptors
3. SH2 binds phosphorylated tyrosine and has STAT with it; STAT is phosphorylated by the activated JAK
4. STAT/SH2 with STAT/SH2 dimerize and dissociate from receptor – translocates to nucleus and binds to DNA

Question 16

NLS

Answer 16

• “nuclear localization signal”
• like a signal peptide that takes a protein to the nucleus