Bacterial PAMP perception by LRR receptor kinases (FLS2/EFR with BAK1)

Arabidopsis detects conserved epitopes of bacterial proteins at the plasma membrane with leucine-rich-repeat receptor kinases (LRR-RKs) that act as pattern recognition receptors (PRRs). FLS2 binds flg22, the conserved N-terminal epitope of flagellin, and EFR binds elf18, the N-terminal epitope of elongation factor Tu. Ligand binding recruits the SERK-family co-receptor kinase BAK1 (SERK3): in the FLS2 complex BAK1 contacts the C terminus of FLS2-bound flg22 and the two kinases activate each other by transphosphorylation. The activated receptor complex phosphorylates receptor-like cytoplasmic kinases (RLCKs) of subfamily VII. BIK1 is phosphorylated by BAK1 within minutes, then directly phosphorylates the plasma membrane NADPH oxidase RBOHD, which together with calcium binding to its EF-hands produces the apoplastic burst of superoxide; BIK1 also promotes the flg22-induced rise in cytosolic calcium. In a second branch, RLCK VII kinases phosphorylate the MAP kinase kinase kinases MAPKKK3 and MAPKKK5, which activate the MAP kinase kinases MKK4 and MKK5 and, through them, the MAP kinases MPK3 and MPK6, which drive defence gene expression. These early events together initiate pattern-triggered immunity against bacteria.

Boundary. The module covers perception of the bacterial peptide PAMPs flg22 and elf18 by the LRR-RK PRRs FLS2 and EFR, co-receptor recruitment of BAK1, and the two immediate RLCK-dependent signalling branches: BIK1 to the RBOHD ROS burst, and RLCK VII to the MAPKKK3/MAPKKK5-MKK4/MKK5-MPK3/MPK6 relay. It ends at activated MPK3/MPK6 and at RBOHD superoxide production. Out of scope: transcriptional outputs (WRKY22/WRKY29, WRKY33 and other MPK3/MPK6 substrates), camalexin synthesis (MODULE:camalexin_biosynthesis, whose MPK3/MPK6-WRKY33 regulatory part sits downstream of this module), callose deposition, stomatal closure, and salicylic acid signalling. The MEKK1-MKK1/MKK2-MPK4 branch, also activated by these PRRs, is not modelled. Receptor endocytosis and turnover (FLS2 internalisation, PUB12/PUB13 ubiquitination, BIK1 turnover, the PP2C38 phosphatase) and the BIR negative regulators are attenuation, not steps of the pathway. Intracellular NLR-mediated effector-triggered immunity is MODULE:plant_nlr_resistosome_signaling. Relation to MODULE:chitin_perception. The fungal chitin pathway uses the same downstream proteins (BIK1, RBOHD, MAPKKK5, MKK4/MKK5, MPK3/MPK6) behind a LysM receptor complex with CERK1 as the kinase and PBL27/RLCK VII-4 kinases as the MAPKKK5 kinase. The shared steps are modelled here again because a module must be self-contained, but they carry the same molecular functions, taken from the same gene reviews, as the chitin module; the MAPK relay in both modules conforms_to MODULE:mapk_relay rather than redefining it. The receptor complex (LRR-RK PRR plus SERK co-receptor) is what is specific to this module. Receptor variant set. FLS2 and EFR are alternative ligand-binding PRRs that share the BAK1 co-receptor and the downstream kinases, so they are modelled as variants (ONE_OR_MORE: both are present in the same cells). Their molecular functions follow the gene reviews, which make different choices: the FLS2 review asserts pattern recognition receptor activity (GO:0038187) and transmembrane receptor protein serine/threonine kinase activity (GO:0004675); the EFR review asserts transmembrane receptor protein kinase activity (GO:0019199) and protein serine kinase activity (GO:0106310, BIK1 phosphorylation). FLS2 is broadly conserved in flowering plants; EFR is restricted to the Brassicaceae, so the module is scoped to Arabidopsis. The other bacterial-pattern LRR-type receptors (e.g. the LRR-RLP RLP23 for nlp20, which uses SOBIR1) and the endogenous Pep receptors PEPR1/PEPR2 also signal through BAK1 and BIK1 but have no gene reviews here and are not added. BAK1. BAK1 carries the same core molecular function (GO:0004675) as in MODULE:brassinosteroid_signaling, where it is the BRI1 co-receptor; its role here is the co-receptor of FLS2 and EFR. SERK4/BKK1 and other SERKs act partly redundantly with BAK1 in PRR complexes but have no gene reviews here. bak1 mutants lose early responses to EF-Tu but not late ones, so BAK1 is not the only route to EFR signalling. RLCK step. BIK1 is the grounded RLCK: it is phosphorylated in an FLS2- and BAK1-dependent manner, and directly phosphorylates RBOHD. Its paralog PBL1 (Q8H186) acts partly redundantly with BIK1 for flg22- and elf18-induced calcium elevation, but its gene review finds no evidence that PBL1 alone phosphorylates RBOHD, so it is named here and not added as a member, matching MODULE:chitin_perception. BIK1 also phosphorylates the calcium-permeable channel OSCA1.3 for stomatal closure (BIK1 review core function); that guard-cell output is outside this boundary. The RLCK VII kinases that phosphorylate MAPKKK5 Ser-599 downstream of FLS2/EFR are not grounded (see knowledge gaps). MAPK relay. Asai et al. 2002 named MEKK1 as the MAP3K upstream of MKK4/MKK5 in flagellin signalling; later work assigns MEKK1 to MPK4 activation and places MAPKKK3 and MAPKKK5 upstream of MPK3/MPK6 (PMID:29871986), so the MAP3K tier is grounded on MAPKKK5 (MAPKKK3 has no gene review). The MAPK relay conforms_to MODULE:mapk_relay. FER is a regulator, not a part. FERONIA (Q9SCZ4) is a malectin-like receptor kinase that facilitates the ligand-induced association of FLS2 and EFR with BAK1, and the RALF23 peptide inhibits this through FER (PMID:28104890). FER does none of the perception or relay steps itself: it acts as a scaffold that modulates complex assembly, and its gene review records immune functions as non-core, with RALF-receptor kinase activity in growth and reproduction as the core functions. It is therefore recorded here as a regulator of the receptor-complex step and is not modelled as a part; see curation follow-ups. FRK1 is a readout, not a part. FRK1 (O64483) is a receptor-like kinase whose transcription is rapidly induced by flg22 downstream of FLS2 and the MAPK cascade, and it is widely used as an early PTI marker gene. Its gene review finds no characterized activity, ligand, substrate or immune loss-of-function phenotype, so it does no step of this pathway; it is an output of the transcriptional programme outside the boundary. Grounding. Gene reviews ground FLS2, EFR, BAK1, BIK1, RBOHD, MAPKKK5, MKK4, MKK5, MPK3 and MPK6 (all ARATH); PBL1, FER and FRK1 are cited in notes. No PANTHER family ids are asserted. No production GO-CAM in gocams/index.tsv contains these proteins. Curation follow-ups (not knowledge gaps). The FER gene review could record the scaffold role in FLS2/EFR-BAK1 complex assembly (PMID:28104890) as a non-core function. MAPKKK3, SERK4/BKK1, the RLCK VII-4 kinases, PEPR1 and RLP23 need gene reviews before they can be added as members. A companion module for the MEKK1-MKK1/MKK2-MPK4 branch could be built once MEKK1, MKK1, MKK2 and MPK4 are reviewed.