BI203 Lecture 21: Cell Signaling - Slides 50-66 (Receptor Protein-Tyrosine Kinases, Ligand-Gated Ion Channels, Cytokine Receptors linked to Tyrosine Kinases) Flashcards
___ ___ ___ (RTKs) - Includes the receptors for most polypeptide growth factors.
Receptor tyrosine kinases
All RTKs have:
- An N-terminal ___ ligand-binding domain.
- A single ___ α helix.
- A ___ C-terminal domain with protein-tyrosine kinase activity.
extracellular, transmembrane, cytosolic
Binding of ligands (___ ___) to the extracellular domains activates the cytosolic kinase domains.
This results in ___ of both the receptors and intracellular target proteins that propagate the signal.
growth factors, phosphorylation
Many RTK ligands (growth factors) function as dimers.
RTK activation begins with ___ ___.
receptor dimerization
The first step is ligand-induced receptor dimerization.
This results in receptor ___, as the two polypeptide chains cross-phosphorylate each other.
autophosphorylation
Autophosphorylation has two effects:
1) Increases ___ ___.
2) Creates ___ ___ for other molecules.
kinase activity, binding sites
Downstream signaling molecules have domains, such as ___, that bind to specific phosphotyrosine-containing peptides of the activated receptors.
SH2
___ ___ ___ stimulate intracellular tyrosine kinases with which they are non-covalently associated.
Non-receptor tyrosine kinases
The ___ ___ superfamily includes receptors for most cytokines and some polypeptide hormones.
cytokine receptor
The structure of cytokine receptors is similar to receptor tyrosine kinases, but the cytosolic domains have ___ catalytic activity.
Ligand binding induces ___ of receptors, and cross-phosphorylation of associated ___ ___ ___.
no, dimerization, Non-receptor tyrosine kinases
The activated kinases then phosphorylate the receptor.
This provides phosphotyrosine-binding sites for
recruitment of downstream signaling molecules which have ___domains.
SH2
The kinases associated with cytokine receptors belong to the ___ ___ (JAK) family.
Janus kinase (JAK)
Key targets of JAK kinases are ___ ___ (signal transducers and activators of transcription).
___ ___ are transcription factors with SH2 domains.
STAT proteins
STAT proteins are inactive in the cytosol until ___ ___ are stimulated.
Then they bind to phosphotyrosine sites on the receptor, and are phosphorylated by ___.
The phosphorylated STAT proteins then dimerize and translocate to the nucleus.
cytokine receptors, JAK
Additional non-receptor tyrosine kinases belong to the ___ family.
These kinases play key roles in signaling downstream of cytokine receptors, receptor tyrosine kinases, antigen receptors on B and T lymphocytes, and receptors involved in cell–cell and cell–matrix interactions.
Src
