RAS Pathway

Information entering the brain along the sensory nerve pathway passes to the sensory cortex. However, nerve branches from the pathway first send impulses to the ascending reticular-activating system or RAS, which stimulates activity and attentiveness throughout the entire cortex. The resultant outgoing information leaves the brain from the motor cortex through the motor pathway and then into the spinal cord.

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Signaling Pathway of Ras. Binding of growth factors to receptor tyrosine kinases stimulates the autophosphorylation of specific tyrosines on the receptors. The phosphorylated receptor then binds to an adaptor protein called GRB2 which, in turn, recuits SOS (son of sevenless) to the plasma membrane. SOS is a guanine nucleotide exchange factor which displaces GDP from Ras, subsequently allowing the binding of GTP (Ras is already anchored to the plasma membrane by post-translationally added lipids, shown as a red line). GTP-bound Ras recruits and activates Raf. Raf initates a cascade of protein phosphorylation by first phophorylating MEK. Phosphorylated MEK in turn phosphorylates ERK. Phosphorylated ERK moves from the cytoplasm into the nucleus where it subsequently phosphorylates a number of transcription factors, including the specific transcription factor called Elk-1. Phosphorylated transcription factors turn on transcription (gene expression) of specific sets of target genes. The activity of Ras is limited by the hydrolysis of GTP back to GDP by GTPase activating proteins (GAP). Other abbreviations are: MEK = MAPK/ERK kinase, ERK = extracellular receptor-stimulated kinase, MAPK = mitogen-activated protein kinase. Kinases are enzymes that add phosphates to molecules using ATP. Mitogens are factors (such as growth factors) that stimulate cell division.