Like GPCRs, enzyme linked receptors are transmembrane proteins, but typically single pass.
The intracellular domain has enzymatic activity or associates directly with an enzyme.
Some subfamilies of receptor tyrosine kinase (RTKs)
RTKs are the most numerous enzyme-coupled receptors (~60 genes)
Activation of receptor tyrosine kinases (RTKs)
Ligand binding causes receptor dimerization bringing the kinase domains of two receptor
Transautophosphorylation on multiple tyrosine residues – higher activity
Phosphorylated RTKs serve as docking sites for intracellular signaling proteins
SH2 and PTB domains within signaling proteins recognize phospho – tyrosine
Formation of a signaling complex that relays the signal onward
Some proteins bind activated RTKs to down regulate them by endocytosis.
Development of cancer when this is not effective.
Ras is a monomeric GTPase that relays signals from RTKs
Has a covalently attached lipid for membrane anchoring
Molecular switch: GTP/GDP. Activated by GEFs, inactivated by GAPs
Can act as a signaling hub
30% of tumors have hyperactive mutant forms of Ras
How an RTK can activate the GTPase Ras? An example from the fly eye
Adaptors and GEFs couple RTK activation to Ras activation Ras activates a mitogen-activated protein (MAP) kinase mod