RAS-RAF-MEK-ERK PATHWAY
MAPK/ERK pathway
EGF -> EGFR -> GRB-2 -> SOS -> RAS -> RAF -> MEK -> ERK -> Transcription Factors -> Cell Proliferation, Survival, Metastasis
ERK
Extracellular Regulated Kinase; activates latent transcription factors like MAPK, c-myc, c-jun, c-fos, ets.
EGF
epidermal growth factor
N-ras
melanomas, hematologic malignancies
B-Raf
serine/threonine kinase over expressed in MELANOMA, Non Hodgkin's lymphoma, colorectal cancer, papillary carcinoma of the thyroid; Point Mutation
RAF
1. 3 variants RAF-A, RAF-B, RAF-C; 2. Regulated by PFK, SRC, HSP90, 14-3-3 3. Phosphorylates MEK1/2 4. Melanoma, Thyroid, Colon Cancer
RAS
1. Has 3 variants H-RAS, K-RAS, & N-RAS; 2.Phosphorylates RAF 3. Thyroid, Colon, Endometrial, Lung Adenocarcinomas, Myeloid Leukemias Cancer.
EGFR
1. epidermal growth factor receptor; 2. Phosphorylates GRB2; 3. Activated by TGFa, EGF, Betacelluim, & Epiregulin. 4. Over-expression = Increased MAPK/ERK pathway 5. Lung, Colorectal, Pancreatic Cancer
RAS drugs
Binimetinib: Inhibits MEK1/2
SOS
Gaunine Nucleotide exchange factor; Phosphorylates RAS
Grb2
Growth factor receptor bound protein 2; binds SOS
K-ras
Lung ca, colon ca, & Pancrease ca
MEK1/2
MItogen Activated Protein Kinase; Phosphorylates ERK
EGFR drugs
Mab: Cetuximab Tinib: Erlotinib, Afatinib
MAPK/ERK pathway
RAS-RAF-MEK-ERK; Goal Cell Proliferation, Survival, Metastasis.
H-RAS
bladder and kidney tumors