How ERK1/2 Activation Controls Cell Proliferation and Cell Death Is Subcellular Localization the Answer?

Activation of receptor tyrosine kinases (RTKs) or G protein-coupled receptors (GPCRs) by growth factors or mitogens leads to the recruitment of an adaptor protein Grb2 (growth factor receptor bound protein) and the guanine nucleotide exchange factor (SOS). The SOS activates Ras to recruit and activate Raf at the plasma membrane by phosphorylation at multiple sites. MEK1/2 is which then phosphorylated at two serine residues that subsequently phosphorylates ERK1/2 on both threonine and tyrosine. Activated ERK1/2 phosphorylates RSK and both RSK and ERK translocate to the nucleus where they activates multiple transcription factors ultimately resulting in effector protein synthesis and causing changes in cell proliferation and survival. ERK phosphorylation of MEK and possibly Raf can inactivate the pathway at those steps creating a negative feedback loop.

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How ERK1/2 Activation Controls Cell Proliferation and Cell Death Is Subcellular Localization the Answer?. () Yohannes Mebratu, et al. Cell Cycle. ;8(8):1168-1175. Figure: F1. All organisms Homo sapiens Mus musculus Rattus norvegicus Drosophila melanogaster

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