ERK1/2 (Ras-RAF-MEK-ERK) MAPK cascade module

A taxon-neutral decomposition of the canonical Ras-RAF-MEK-ERK mitogen-activated protein kinase cascade, the concrete ERK1/2 realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). The cascade converts receptor-proximal tyrosine-phosphorylation events into ERK1/ERK2 activity and a proliferative/differentiation transcriptional program, and is deployed downstream of many distinct receptor systems: receptor tyrosine kinases (EGFR, FGFR, PDGFR, insulin/IGF), cytokine receptors signaling through JAKs, G-protein-coupled receptors, and integrins. The module captures: (1) recruitment of SH2/SH3 adaptors (GRB2, SHC) to a receptor phosphotyrosine; (2) GRB2-mediated recruitment of the Ras guanine nucleotide exchange factor SOS; (3) the Ras nucleotide switch (SOS GEF -> Ras GTPase -> RasGAP), declared as an inner bundle that `conforms_to` gtpase_switch; (4) the conforming ERK kinase relay - Ras-driven RAF(MAP3K) -> MEK1/2(MAP2K) -> ERK1/2(MAPK) on the TEY motif - declared as an inner bundle that `conforms_to` mapk_relay; (5) ERK action on nuclear (ELK1/Ets, RSK, MSK) and cytoplasmic substrates to drive transcription, proliferation, and differentiation; and (6) DUSP/MKP negative feedback on ERK. Grounded in GO:0000165 (MAPK cascade) / GO:0070371 (ERK1 and ERK2 cascade).

This module is the concrete ERK1/2 branch of the generic three-tier MAP kinase relay (MODULE:mapk_relay), and embeds two nested conforming bundles: the inner `erk_relay` node bundles the RAF -> MEK -> ERK tiers and conforms to mapk_relay, and the inner `ras_nucleotide_switch` node bundles the SOS GEF -> Ras GTPase -> RasGAP tiers and conforms to MODULE:gtpase_switch. The receptor-proximal adaptor step and the downstream ERK-output and DUSP-feedback steps are this cascade's free extensions around the conforming cores. The module is intentionally a reusable "sidecar": it is deployed downstream of many receptor systems rather than being specific to one. It is referenced as a branch-point interface by the JAK-STAT signaling module (MODULE:jak_stat_signaling), where JAK-phosphorylated receptor tyrosines recruit GRB2/SHC and fork into this cascade in parallel with STAT activation; ERK in turn feeds back onto STATs via C-terminal serine phosphorylation. The same module is deployed by RTKs, GPCRs (often via PI3K/PKC or transactivation), and integrins. Representative UniProt members were verified against curated reviews in this repository; tiers without a verified local exemplar are given as family descriptors with preferred_term and description.