part 3 of day II Flashcards
plasma membrane receptors
have extacellular domain, an alpha-helical transmembrane domain, and an intracellular domain.
plasma membrane explain
upon binding of the ligand to the extra cellular domain the receptors undergo a conformation change that “activates the intracellular domain”
Activation can occur as the opening of a channel in the membrane, activation of an enzymatic activity in the receptor, and/or a change in the binding of intracellular proteins in the intracellular domain
neuromuscular junction
this receptor is a ligand-activated ion channel. when open it specifically allows Na+ and K+ ions to flow in the direction of their concentration gradient
receptors that are kinases
A tyrosine kinase receptor
tyrosin kinase receptor is activated upon ligand binding to phosphorylate itself on centertain tyrosine residues (auto-phosphorylate) and/or to phosphorylate other associated proteins
kinases
put phosphate group on receptors
serine/threonine kinase receptors
receptors that are kinase
activated by ligand binding to phosphorylate itself and other proteins on serine and/or threonine residues, e.g. some cytokine receptors
receptors that are kinases
A tyrosine kinase receptor
The proteins that bind phosphorylated receptors are often complexed with other proteins that have enzymatic activities.
The binding event often activates the proteins in these complexes
receptors that are kinases
example: MAP kinase signaling
A tyrosine kinase receptor
The binding of Grb2 to the growth factor receptor stimulates the associated protein Ras to exchange GDP for GTP and form a complex with a different protein, Raf.
Binding of Ras-GTP to Raf, activates a kinase activity in Raf that phosphorylates another kinase, which is activated to phosphorylate another kinase, etc….
The phosphorylation of these transcription factors activates them to bind target genes and
alter their rate of transcription
activate MAP kinase singaling
What is referred to kinase cascade
MAPK signaling
A tyrosine kinase receptor
This is referred to as a kinase
cascade which eventually leads to transcription factors in the cell nucleus.
Key concepts for receptor that are kinases
MAPK signaling
A tyrosine kinase receptor
For plasma membrane receptors the signal is transduced to the nucleus by other proteins.
examples of a receptor that are kineses in real-life importance
MAPK signaling
A tyrosine kinase receptor
MAPK signaling is often amplified in cancer; it is either hyperactivated or can’t be terminated.
Many tumors are found to have acquired mutations in the gene encoding Ras so that the protein fails to be deactivated.
Persistent MAPK signaling causes unregulated cell proliferation.
Inhibitors of the Raf protein are FDA-approved and used in the treatment of particular cancers.
Trametinib is an approved MEK inhibitor
Ras and Raf are considered
MAPK signaling
A tyrosine kinase receptor
Ras and Raf are considered oncogenes.
