Question

How do RTKs transduce signal from outside the cell into the cytoplasm? Specifically, " How do growth factor receptors use their tyrosine kinase domains to emit signals in response to ligand binding?" Please use diagrams, labels and descriptions to answer.

Answer 1

The RTK signal transduction pathway was one of the first pathways to various areas of developmental biology. A researcher studying Drosophila eyes, nematode vulvae, and human cancers found that they were all studying the same genes. The RTKs pathway begins at the cell surface where a receptor tyrosine kinase (RTK) binds its specific ligand. Ligands that bind to RTKs include the fibroblast growth factors epidermal growth factors platelet-derived growth factors, and stem cell factor. Each RTK can bind only one or a small set of these ligands. The RTK spans the cell membrane, and when it binds its ligand, it undergoes a conformational change that enables it to dimerize with another RTK. This conformational change activates the latent kinase activity of each RTK and these receptors phosphorylate each other on particular tyrosine residues. Thus, the binding of the ligand to the receptor causes the autophosphorylation of the cytoplasmic domain of the receptor. Without the gap protein, RAS protein can not catalyze GTP as well as active configuration.

The phosphorylated tyrosine on the receptor is then recognized by an adaptor protein so the adaptor protein serves as a bridge that links the phosphorylated RTK to a powerful intracellular signaling system while binding to the phosphorylated RTK through one of its cytoplasmic domains the adaptor protein also activates a G protein. Normally the G protein is in an inactive GDP-bound state. The activated receptor stimulates the adaptor protein to activate the guanine nucleotide releasing factor. This protein exchanges a phosphate from a GTP to transform the bound GDP into GTP. The GTP-bound G protein is an active form that transmits the signal. After giving the signal the GTP on the G protein is hydrolyzed back into GDP. This catalysis is greatly stimulated by the complexing of the Ras protein with the GTPase-activating protein. In this way, the G protein is returned to its inactive state where it can await further signaling. One of the major G proteins is called Ras mutations in the RAS gene account for a large proportion of human tumors and the mutations of RAS that make it oncogenic all inhibit the binding of the GAP protein.