neurotropic factor neurotropic factor
Further work identified the pathways by which interaction with these cell surface receptors resulted in growth and proliferation of cells. There are various mechanisms by which these processes occur, but a generalized pathway involves interaction of a growth factor with a growth factor receptor occurring as a monomer present in the phospho-lipid bilayer of the cell membrane, which results in dimer-ization of the receptors (Scheme 10.31). The receptors themselves possess an extracellular-binding domain for interaction with the growth factors, an intracellular domain, and a connecting transmembrane region. The intracellular domain of these receptor proteins often function as kinases, many of which are TKs that phosphorylate residues on the other monomer receptor. The resulting phosphorylated residues are recognized by the Src homology 2 domain (SH2) of cytoplasmic proteins such as Shc, Grb-2, and Sos, which activate Ras. These cytoplasmic proteins then serve to transmit the growth signals from the growth factor receptors to Ras (Fig. 10.25). Ras is a G protein tethered to the cytoplasmic membrane, which may bind GTP resulting in activation of Ras or bind GDP resulting in Ras inactivation. Ras also normally has the ability to hydrolyze GTP to inactivate itself. Many cancers are found to have altered forms of Ras, which is present in a hyperactive state. Ras, in its activated form activates a series of kinases, many of which are TKs with various effects on cells. Notable is the Ras-Raf-MEK-ERK pathway also known as the mitogen-activated protein kinase (MAPK) pathway. This is a
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