What are the 5 well-known enzyme-linked cell surface receptors?
1. Receptor Guanylyl Cyclase: produces cGMP
2. RTK: phosphorylate tyrosine residues
... [Show More] leading to association of signalling molecules and cascade
3. TK Associated Receptors: associate with proteins having TK activity
4. Receptor Tyrosine Phosphates: Removes phosphate on tyrosine residues
5. Receptor Serine/Threonine Kinases: phosphorylate specific Serine/Threonine residues on IC signalling molecules
How are RTK and TK Associated Receptors different?
RTK phosphorylate tyrosine while associated receptors bind/find proteins with TK activity to initiate the cascade of signalling.
What is the reciprocal of RTK?
Receptor Tyrosine Phosphatases. They take the phosphate off the tyrosine residues to inactivate signalling cascades.
Ex. Transforming GF Beta superfamily of receptors, cell type dependent.
What is the major mechanism for receptor signal transduction?
Tyrosine kinase phosphorylation
RTK vs. Serine/Threonine Phosphorylation ?
Tyrosine phosphorylation is rare (1%) relative to serine/threonine residue phosphorylation. Tyrosine phosphorylation is the major mechanism of receptor signal transduction.
What is the net effect of activated TKs?
Tyrosine phosphorylation on target proteins.
What do TK pathways mediate?
Cell growth (growth factors), differentiation, host defense, metabolic regulation, cell survival pathways (survival factors).
What are amplifiers of the TK pathways?
PI3-K -> PIP3
PLC -> DAG and InsP3&Ca2+
What are RTK mediated actions in the cell?
regulation of cell proliferation, differentiation, and cell motility, promotion of cell survival and modulation of cellular metabolism.
TKs exist in either the cytosol or as transmembrane receptors, what are the differences in the two types?
Cytosol receptors have an src N-terminal region. Cytosol has no membrane spanning domain.
TM receptor has a single membrane spanning hydrophobic TM domain. Ex) Epidermal GF RTK.
What is src?
Src is a non-receptor TK, so it does not span a membrane. It is a tyrosine kinase. And although it is cytoplasmic TK it can still bind to activated RTKs.
What is contact inhibition confluency?
Stops Src domains signalling and therefore cells stop dividing.
If there is an issue then cancer can result and mutation causes an inhibition of the stop signal so the cells keep growing and dividing.
What are SH domains?
Src homology domains. Src and other proteins that have src-homology domains can bing to activated RTKs.
What are the different SH domains in proteins?
There are SH1, SH2 and SH3 domains. [Show Less]