{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

(25) 921-946 enzyme coupled receptors

(25) 921-946 enzyme coupled receptors - S IGNAL ING THROUGH...

Info iconThis preview shows pages 1–3. Sign up to view the full content.

View Full Document Right Arrow Icon
SIGNALING THROUGH ENZYME COUPLED CELL SURFACE RECEPTORS Activated receptor tyrosine kinases phosphorylate themselves o GPCRs are transmembrane proteins o Enzyme-coupled receptors are also transmembrane proteins o Enzyme-coupled receptors have their ligand binding domain on the outer surface of the membrane o GPCR has 7 transmembrane segments o Enzyme-coupled receptor has only one o There are 6 classes of enzyme-coupled receptors: Receptor tyrosine kinases Directly phosphorylate tyrosines on themselves Tyrosine-kinase associated receptors Directly recruit cytoplasmic tyrosine kinases to relay the signal Receptor serine/threonine kinases Directly phosphorylate specific serines or threonines on themselves o Many extracellular signal proteins act through RTKs o For a GPCR, ligand binding changes the orientation of several of the transmembrane alpha helices, shifting position of loops o But for RTKs, ligand binding causes the receptor chains to dimerize, bringing the kinase domains of 2 receptor chains together so that they can become activated and cross-phosphorylate each other on multiple tyrosines (transautophosphorylation) o Ligand binding causes the two green receptors to dimerize, then the 2 kinase domains cross-phosphorylate each other, increasing the activity of the kinase domains, which now phosphorylate other sites on the receptors
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
o Dominant-negative regulation – one of the tyrosine kinase domains is mutant and doesn’t work Phosphorylated tyrosines on RTKs serve as docking sites for intracellular signaling protein o Phosphorylation of tyrosines within the kinase domain increases the kinase activity of the enzyme o Phosphorylation of tyrosines outside the kinase domain creates high- affinity docking sites for the binding of specific intracellular signaling proteins, which bind to the RTK o Binding to RTK activates the docked signaling protein o Use IRS1 to create more docking sites Proteins with SH2 domains bind to phosphorylated tyrosines o These proteins help to relay the signal onwards.
Background image of page 2
Image of page 3
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}