BIO 320 Chapter Notes - Chapter 15: Phosphoinositide 3-Kinase, Ephrin Receptor, Protein Kinase
Chapter 15 Cell Signaling: Cell Signaling III (pg. 857-864)
• Scaffold proteins help prevent cross-talk between parallel MAP kinase modules
o Different modules mediate different responses
▪ Some use the same kinases but still manage to activate different effector
proteins for different responses
o Cells prevent cross-talk between MAP kinase modules with scaffold proteins
▪ Scaffolds bind all or some of the kinases into a complex to ensure response
specificity
▪ Present in both yeast and mammal cells
• In mammals, at least five parallel MAP kinase modules can operate in a
cell at a time
o But scaffold strategy reduces opportunities for amplification of the signal and spreading
to other parts of the cell
▪ Unknown to what extent the components can dissociate from the complex
• Rho family GTPases functionally couple cell-surface receptors to the cytoskeleton
o Rho family – large cell-surface receptor family besides Ras
▪ Regulates actin and microtubule cytoskeleton plus cell cycle progression, gene
transcription, and membrane transport
▪ Also mediates cytoskeleton responses for cell migration and axon outgrowth
o Rho, Rac, and Cdc42 – best characterized Rho family members
o Also activated/inactivated by GEFs/GAPs
▪ Soe GEFs/GAPs are speifi for a faily eers, others are’t
o Inactive Rho family members usually bound to guanine nucleotide dissociation inhibitors
(GDIs) in cytosol rather than membrane like Ras
▪ Prevents interaction with GEFs in plasma membrane
o Ephrin – example of RTKs activating a Rho GTPase
▪ Activates Eph family of RTKs
▪ Ephexin – Rho-GEF that the Eph receptor response depends on
• Stably associate with cytosolic tail of Eph receptor
• PI-3 kinase produces lipid docking sites in the plasma membrane
o Phosphoinositide 3-kinase (PI-3 kinase)
▪ Phosphorylates inositol phospholipids instead of proteins
o Phosphatidylinositol (PI) – unique in that it can undergo reverse phosphorylation to
produce phosphoinositides
o PIP3 can serve as docking site for various intracellular signaling proteins, which can
assemble into signaling complexes
o Phosphoinositide phosphatases – dephosphorylate the PIP2
o Various types of PIP 3-kinases
▪ Class I – activated by RTKs and GPCRs
• Heterodimers composed of common catalytic subunit and different
regulatory subunits
• Class Ia PI-3 kinases – activated by RTKs
• Class Ib PI-3 kinases – activated by GPCRs
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