LIFE 210 Lecture Notes - Growth Factor, Janus Kinase, Gtpase
Document Summary
Like gpcrs, enzyme linked receptors are transmembrane proteins, but typically single pass. The intracellular domain has enzymatic activity or associates directly with an enzyme. Rtks are the most numerous enzyme-coupled receptors (~60 genes) Ligand binding causes receptor dimerization bringing the kinase domains of two receptor chains together. 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. 30% of tumors have hyperactive mutant forms of ras. Adaptors and gefs couple rtk activation to ras activation. Ras activates a mitogen-activated protein (map) kinase module. Scaffold proteins help prevent cross-talk between parallel map kinase modules.