CaMKII is a family of multifunctional protein kinases that activates signaling pathways. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. CaMKII downstream targets that may be involved in regulation of neuronal viability. CaMKII signaling may promote excitotoxic cell death or neuronal survival . Activation or inhibition of the downstream targets is indicated. Some but not all of these downstream effects are mediated by direct phosphorylation of the target.
Currently there are three distinct MAP kinase activation pathways described in mammals: ERK1/2 MAP kinase pathway, Jun pathway and p38 MAP kinase pathway. MAP kinases regulate functions of several substrates through phosphorylation, including a family of protein kinases named MAPK activated protein kinases (MAPKAPKs), phosphates and transcription factors.
The MAPK signalling pathway consists of individual components, called MAP kinases. Activation of the MAPK signalling pathway comprises four levels of regulation by phosphorylation : the first, where a MAP3K becomes activated by transfer of a phosphate group onto the serine or threonine residue within its activation loop. This kinase then phosphorylates the serine residue within the activation loop of the MAP2K, thereby activating the kinase.
The receptors for many polypeptide growth factors and hormones are proteins with a single transmembrane domain and an intrinsic tyrosine kinase activity. Those receptors include epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). Insulin-like growth factor receptor (IGFR), a dimeric receptor, is also another tyrosine kinase receptor. Human epidermal growth factor receptor (HER) is one member of a family of four related proteins, termed the ErbB/HER receptors (because of their similarity to the v-ErbB oncogene of avian erythroblastosis virus that induces erythroid leukemia in birds). The link of ErbB2/HER2 with cancer is also observed in human, as overexpression of the human ErbB2 gene, which encodes the human EGFR (also known as HER2), is related with cancer. GRB2 is a protein that contains SH2 and SH3 domains and can form a bridge between the receptor and a guanine exchange factor (GEF), which is able to exchange GDP for GTP in a GTP activating protein (GAP). SOS (son of sevenless) is the main Ras GTPase-activating protein (RasGAP). Thus, SOS activates Ras.