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Joined 2026-09-21 Message
Incoming links: SH2 domain
Insulin receptor substrate 2026-10-14
An insulin receptor substrate is a docking protein phosphorylated by the activated insulin receptor. Its phosphotyrosine residues recruit downstream signaling proteins, including SH2 domain-containing components of phosphoinositide 3-kinase. This connects reception to the pathway described under insulin, rather than making the insulin receptor substrate another extracellular ligand.[ref]
Cell signaling by receptor-tyrosine kinases by Mark A Lemmon and Joseph Schlessinger. “Linking RTK activation to cell signaling”: IRS docking proteins and Figure 3A
Phosphotyrosine residue 2026-10-14
A phosphotyrosine residue is a tyrosine residue modified by phosphorylation. Its location and surrounding protein primary structure help determine which SH2 domains can recognize it.
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