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Incoming links: Protein domain
Receptor tyrosine kinase Created 2026-10-14 Updated 2026-10-20
A receptor tyrosine kinase combines extracellular ligand recognition with an intracellular protein kinase protein domain. A membrane-spanning segment connects these parts across the cell membrane: the signal changes the intracellular machinery without requiring the ligand to enter the cytosol. The protein kinase transfers a phosphate group from ATP to selected tyrosine residues on proteins, including the receptor itself.[ref]
Signaling through Enzyme-Linked Cell-Surface Receptors. “Activated Receptor Tyrosine Kinases Phosphorylate Themselves”: extracellular binding, intracellular catalytic domains and ATP-dependent phosphate transfer
This architecture makes a reception event useful in two ways: it can change catalytic activity and assemble a local group of signaling proteins. Trans-autophosphorylation can create phosphotyrosine residues recognized by SH2 domains. Recruitment positions a downstream enzyme or relay protein near its partners. Neither every modified site nor every recruited protein has the same effect; association is a specific molecular connection, rather than a universal command to activate everything nearby.[ref]
Signaling through Enzyme-Linked Cell-Surface Receptors. “Phosphorylated Tyrosines Serve as Docking Sites For Proteins With SH2 Domains”, Figure 15-53: signaling enzymes, adaptors and negative regulators
Compare the epidermal growth factor receptor with the insulin receptor. Their common topology does not impose one activation geometry or make assembly equivalent to activity. The receptor phosphorylation assay consequently needs more than evidence that two protein chains associate.
Receptor tyrosine kinase architecture and distinct activation mechanisms
. Original topology cartoons contrasting EGFR with the preassembled insulin receptor. Orange dots mark phosphotyrosine residues; S–S marks protein disulfide bonds. The EGFR panel separates asymmetric catalytic contact from partner-tail phosphorylation. Shapes, distances and drawn ligand counts are explanatory, rather than atomic structures or binding stoichiometry. Details.
SH2 domain Created 2026-10-14 Updated 2026-10-20
An SH2 domain is a protein domain that recognizes a phosphotyrosine residue together with surrounding sequence features. This selective binding recruits a protein to a modified receptor or docking protein; it does not itself imply catalysis.[ref]
Signaling through Enzyme-Linked Cell-Surface Receptors. “Phosphorylated Tyrosines Serve as Docking Sites For Proteins With SH2 Domains”, Figure 15-53
Topology of membrane compartments 2026-10-20
Ordinary vesicle budding and fusion preserve which side of a membrane a protein domain faces: a cytoplasmic domain remains cytoplasmic, and a luminal domain remains luminal. Invagination can enclose previously external space without transporting its contents through a bilayer. The endoplasmic reticulum lumen is continuous with the space between the two nuclear envelope membranes; it is not the chromosome-containing nucleoplasm. Any proposed evolutionary remodelling must account for these distinct spaces and the membrane connections between them.