Lecture 24 - Cancer Genetics 2 (Signaling Pathways and Intervention) Flashcards
Which is NOT a function of SH2 domain containing proteins?
A. Recruit SH2 proteins to the plasma membrane
B. Provide docking sites for association with other proteins
C. Bind proline rich sequences of 9 or 10 residues
D. Promote phosphorylation of associated proteins
E. Stimulate enzyme activity of associated proteins
C. SH3 domains are a second motif of SOME proteins that dock to activated RTKs, and these bind proline rich sequences.
___________ are the largest family of enzyme linked receptors.
Receptor tyrosine kinases
The most common amino acids phosphorylated by protein kinases are ______ and ______.
- serine
- threonine
*Note: phosphorylation of tyrosine occurs less frequently
The structure of tyrosine kinase receptors has 3 major parts. What is the function of the N-terminal?
Extracellular ligand binding domain
The structure of tyrosine kinase receptors has 3 major parts. What is the function of the C-terminal domain?
Cytosolic; protein tyrosine kinase activity
The structure of tyrosine kinase receptors has 3 major parts. What are they?
- N-terminal (extracellular ligand binding domain)
- Single ‘transmembrane’ domain
- C-terminal (cytosolic site of protein TK activity)
Most receptors are ____(a)____ but some receptors, such as ___(b)___ are dimers consisting of two polypeptide chains.
a) monomeric
b) insulin
The process in which a ligand binds to the extracellular domain of the RTK and cross-links the receptor is called:
dimerization
The 2 main types of ligand induced dimerization are:
- auto-phosphorylation
2. cross phosphorylation
Ligand induced dimerization serves to: (2 functions)
- increase receptor kinase activity
2. create binding sites for specific proteins that transduce the intracellular signal
_____(a)_____ are binding sites for a unique set of intracellular proteins that utilize select domains called ____(b)_____.
a) Phosphotyrosine sites
b) SH2 domains
What protein generates diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3)?
Phospholipase C-gamma
Which product generated by phospholipase C-gamma (PLC-gamma) functions to activate serine/threonine protein kinases?
DAG
Which product generated by phospholipase C-gamma (PLC-gamma) binds to ligand-gated Ca2+ channel receptors triggering release of intracellular stores of Ca2+ from the ER?
IP3
The ________ pathway activates RTKs by mobilizing a family of serine/threonine protein kinases.
MAPK
The founding member of the MAPK family is the _______.
extracellular signal regulated protein kinase 1/2 (ERK-1/2)
The Ras proteins belong to the large super family of:
monomeric GTPases
The Ras proteins contain a covalently attached prenyl group that helps to perform what function?
Anchor the protein in the membrane
The Ras protein cycles from __(a)__ to __(b)__.
a) GDP bound inactive form
b) GTP bound active form
What are the two classes of signaling proteins that regulate Ras activity?
- GAPs (GTPase-activity proteins)
2. GEFs (guanine nucleotide exchange factors)
What is the function of GEF signaling proteins?
Activate Ras - promote exchange of bound nucleotide by stimulating loss of GDP.
______ increase the rate of hydrolysis of bound GTP by Ras, thereby inactivating it.
GAP signaling proteins
Which of the following is FALSE regarding non-receptor tyrosine kinases?
A. They are receptors for growth factor signaling
B. They are associated with receptors
C. They phosphorylate target proteins
D. All of the above are TRUE.
A. Non-receptor tyrosine kinases are NOT receptors for growth factor signaling.
_______ receptors act by stimulating intracellular non-receptor tyrosine kinase pathways.
Cytokine