Cytoplasmic Signaling Circuitry

Question 1

RTKs are linked to many different pathways that, collectively, will typically lead to:

Answer 1

• Stimulation of cell proliferation
• Stimulation of protein synthesis
• Inhibition of apoptosis
• Alteration of cytoskeleton

Question 2

Signaling through RTKs

Answer 2

● Receptor dimerization, ligand binding, and transphosphorylation
● RTKs can exist as monomers in an inactive state or as inactive predimers or larger scale clustering
● Ligand binding promotes receptor dimerization and induces conformational reorganization in existing dimers, leading to activation of protein kinase activity

Question 3

SRC kinases

Answer 3

● Non-receptor tyrosine kinases
● Src can be activated by many transmembrane proteins including adhesion receptors, RTKs, GPCRs, and cytokine receptors.
● Src can interact with many proteins by phosphorylation of their tyrosine residues

Question 4

SRC kinases: domain structure

Answer 4

● Src contains 6 domains, 3 “Src Homology domains”
♦ SH1: catalytic domain for tyrosine kinase activity
♦ SH2: “receptor” for a specific phosphotyrosine + C-terminal-flanking oligopeptide sequence.
Allows for protein-protein interactions & protein localization
♦ SH3: Binds to certain proline-rich domains in partner proteins

Question 5

How does the SH2 domain facilitate connecting steeps in the pathway?

Answer 5

1. Ligand binds RTK resulting in transphosphorylation of many Tyr residues
2. Different phosphorylated tyrosines bind (recruit) different SH2-containing proteins
3. Each SH2-containing protein controls a signaling cascade
4. Influence different cell behaviors

Question 6

When EGF receptor bind to the ligand..

Answer 6

a constellation of phosphotyrosine is formed