Ras Pathway

Ras is a GTPase that is anchored to the intracellular side of the plasma membrane through its post-translational lipid modifications. Upon stimulation by growth factors, cytokines, neurotransmitters, or other signals, receptor tyrosine kinases on the cell surface will be autophosphorylated. This causes adaptor protein GRB2 to recruit SOS, a guanine nucleotide exchange factor, which then facilitates binding of GTP to Ras. GTP-bound Ras activates Raf to trigger a phosphorylation cascade involving mitogen-activated protein kinases (MEKs). This ultimately results in the translocation of ERK to the nucleus where it phosphorylates and activates a number of transcription factors like Elk1, initiating expression of genes that promote cell survival and growth. Antigen binding to the T cell receptor (TCR) can also lead to Ras signaling through activation of phospholipase C (PLC) and protein kinase C (PKC). Ras activated by this mechanism drives the PI3K pathway to initiate expression of cell growth genes.

 

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