Identifiers
mitogen-activated protein kinase kinase 1
HUGO:MAP2K1 hgnc_id:HGNC:6840 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750
mitogen-activated protein kinase kinase 2
HUGO:MAP2K2 hgnc_id:HGNC:6842 HGNC:6842 ENTREZ:5605 UNIPROT:P36507
Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / CORE
References
CASCADE:FGF
CASCADE:EGFR
GASCADE:IGF1R
PMID:16227978
Ras GTPases comprise a large family of mostly membrane-resident proteins that shuttle between an inactive GDP-bound and active GTP-bound conformation105. The best-characterized family members are K-Ras, H-Ras and N-Ras.
RasGTP can bind to a number of effector molecules, including the serine/threonine kinase Raf, phosphatidylinositol 3-kinase, RalGDS and others106. RasGTP recruits these proteins to the membrane compartment, which is crucial for their activation and signalling function. All three Raf family members, A-Raf, B-Raf and Raf-1, bind RasGTP as the first step in their activation process. Whereas RasGTP association might suffice to activate B-Raf, both Raf-1 and A-Raf undergo a complex series of activation steps that have not been entirely elucidated and involve changes in phosphorylation levels and protein interactions. For recent reviews on Raf isoforms and their activation mechanisms see Refs 1???3. All Raf isoforms can activate MAPK and ERK kinase (MEK) by phosphorylating two serines in the MEK ACTIVATION LOOP,
PMID:10567412; PMID:15567848
EGFR activates ERK via GRB2/SOS/RAS/RAF pathway