Biology 2382B Lecture Notes - Lecture 9: Rous Sarcoma Virus, Insulin Receptor Substrate, Transmembrane Domain
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After the rtk has dimerized and self-phosphorylated its tyrosines, adapter proteins are required to activate ras, a gtpase which signals further downstream kinases: signalling that is done wrong is the root cause of many human cancers. First, two ligands must bind to two separate receptors. Once this occurs, the receptors can dimerize, creating an active tyrosine kinase domain in the cytosolic region: trans-autophosphorylation occurs where the active tyrosine kinase domain can take atp and phosphorylate the opposite protein at their tyrosine. The opposite protein will reciprocate with phosphorylation: phosphorylation initially occurs on the tyrosines of the activation lip (i. e. it is the first place to be phosphorylated). After the lip tyrosines are phosphorylated, the other tyrosines in the cytosolic domain are phosphorylated as well. Different rtks will have different number of tyrosines they require to be phosphorylated: the phosphotyrosines (phosphorylated-tyrosines) act as docking sites for adapter proteins that contain sh2 or ptb domains.