AdooQ BioScience

Ras pathways: signal transduction pathways IN mammalian cells. The Ras pathway leading into the downstream MAPK pathway. A growth factor (such as epidermal gro...wth factor) binds its receptor, bringing together the chains, which, as in the STAT case, then phosphorylate each other. This phosphorylation recruits an adaptor protein called Grb2, which has an SH2 domain that recognizes a phosphorylated tyrosine residue in the activated receptor. The other end of Grb2 binds SOS, a guanine nucleotide exchange factor (Ras GEF). SOS, in turn, binds the Ras protein, which is attached to the inside face of the cell membrane. Ras is a small GTPase, a protein that adopts one conformation when bound to GTP and another when bound to GDP; interaction with SOS triggers Ras to exchange its bound GDP for a GTP and hence undergo a conformational change. In this new conformation, Ras activates a kinase at the top of the so-called MAPK cascade. The first kinase in this pathway is called a MAPK kinase kinase (MAPKKK) (Raf ); once activated by Ras, this phosphorylates serine and threonine residues in the next kinase (a MAPK kinase [MAPKK], called Mek). This activates Mek, which, in turn, phosphorylates and activates the MAPK (Erk). This MAPK then phosphorylates several substrates, including transcriptional activators (e.g., Jun) that regulate a number of specific genes, including interferon-b See more

The Wnt signaling pathways are a group of signal transduction pathways made of proteins that pass signals into a cell through cell surface receptors. Three Wnt ...signaling pathways have been characterized: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three pathways are activated by binding a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dishevelled protein inside the cell. The canonical Wnt pathway leads to regulation of gene transcription, and is thought to be negatively regulated in part by the SPATS1 gene. The noncanonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell. The noncanonical Wnt/calcium pathway regulates calcium inside the cell. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans. This pathway's clinical importance was demonstrated by mutations that lead to various diseases, including breast and prostate cancer, glioblastoma, type II diabetes and others

New HHMI Research: HHMI Investigator David Liu and colleagues report that a single treatment involving the injection of a genome editing cocktail prevented prog...ressive hearing loss in young mice that would have otherwise gone deaf. While the implications for treating humans are unclear, this work could help inform a development of a cure for certain forms of genetic hearing loss in humans. See more