YODA (YDA; MAPKKK4) is a large Raf-like/MEKK-type mitogen-activated protein kinase kinase kinase with an N-terminal autoinhibitory regulatory domain, a central Ser/Thr kinase domain and a C-terminal extension. It is the MAPKKK that relays signals from cell-surface receptors to the MKK4/MKK5-MPK3/MPK6 module during development. In the leaf epidermis YODA acts downstream of the EPF2/EPF1 peptides perceived by ERECTA-family receptor kinases with TMM and SERK co-receptors, phosphorylating and activating MKK4/MKK5, whose targets MPK3/MPK6 phosphorylate and destabilize the bHLH transcription factor SPEECHLESS and its partner SCREAM, thereby repressing stomatal lineage entry and enforcing stomatal spacing; null yda mutants form epidermes composed almost entirely of clustered stomata, while constitutively active YODA eliminates stomata. YODA is recruited to the cell cortex of asymmetrically dividing stomatal precursors by the polarity scaffold BASL, forming a polarized BASL-YODA-MPK3/6 feedback module, and is inhibited by the brassinosteroid-regulated GSK3 kinase BIN2. The same cascade controls elongation of the zygote and extra-embryonic suspensor fate downstream of SHORT SUSPENSOR, and inflorescence architecture downstream of ERECTA.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of participation in a MAPK cascade for the MEKK-family node. Reason: Core process. YODA is the MAPKKK of the YDA-MKK4/MKK5-MPK3/MPK6 cascade. Supporting Evidence: PMID:17259259 We further establish that the MKK4/MKK5-MPK3/MPK6 module is downstream of YODA, a MAPKKK. |
| GO:0004709 MAP kinase kinase kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of MAP kinase kinase kinase activity. Reason: Core molecular function; YODA phosphorylates the MAPKK MKK4. Supporting Evidence: PMID:22307275 BIN2 phosphorylates YDA to inhibit YDA phosphorylation of its substrate MKK4 |
| GO:0004709 MAP kinase kinase kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC 2.7.11.25 mapping to MAP kinase kinase kinase activity. Reason: Consistent with experimental evidence that YDA phosphorylates MKK4. Supporting Evidence: PMID:22307275 BIN2 phosphorylates YDA to inhibit YDA phosphorylation of its substrate MKK4 |
| GO:0005515 protein binding | IPI PMID:22307275 Brassinosteroid regulates stomatal development by GSK3-media... | MODIFY | Summary: YDA binds the GSK3-like kinase BIN2 (Q39011), which phosphorylates and inhibits it. Reason: The interaction is a direct kinase-substrate interaction with the BIN2 kinase; protein kinase binding is more informative than generic protein binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:22307275 demonstrating direct YDA binding to BIN2 in vitro |
| GO:0005515 protein binding | IPI PMID:25843888 The BASL polarity protein controls a MAPK signaling feedback... | MODIFY | Summary: YDA interacts with MPK6 (BiFC) in stomatal lineage cells. Reason: Interaction of the MAPKKK with the downstream MAP kinase MPK6 within the polarized BASL module; protein kinase binding is the informative term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25843888 The recovered YFP signal suggests that DNyda interacts with MPK6 in vivo, and importantly, in a similarly polarized pattern of BASL |
| GO:0005515 protein binding | IPI PMID:25843888 The BASL polarity protein controls a MAPK signaling feedback... | REMOVE | Summary: YDA binds the phosphorylated polarity scaffold BASL (Q5BPF3) via MAPK-docking motifs. Reason: Generic protein binding is uninformative; BASL is the scaffold, and the functional consequence (polarized cortical recruitment of YDA) is captured by the cell cortex annotation. Removal does not imply the interaction is false. Supporting Evidence: PMID:25843888 We demonstrate that YDA physically interacts with BASL and localizes to the cell cortex of stomatal ACD cells. |
| GO:0005515 protein binding | IPI PMID:28821747 The integration of GΞ² and MAPK signaling cascade in zygote d... | REMOVE | Summary: YDA interacts with the plasma-membrane pseudokinase SHORT SUSPENSOR (SSP/BSK12; Q7XJT7). Reason: Generic protein binding is uninformative; SSP is an inactive pseudokinase, so protein kinase binding would overstate the interaction. The biological relevance is captured by suspensor development. Supporting Evidence: PMID:28821747 YDA interacts with the plasma membrane associated SHORT SUSPENSOR (SSP) through its N- and C-terminal region in vitro and in vivo. |
| GO:0005515 protein binding | IPI PMID:32240168 The MAPK substrate MASS proteins regulate stomatal developme... | REMOVE | Summary: YDA interacts with a MASS protein (AT1G15400) in a stomatal-lineage study. Reason: Generic protein binding without an informative molecular function. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding inferred from the kinase domain. Reason: Required for kinase catalysis. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of cytoplasmic localization. Reason: YODA is a cytoplasmic kinase that is concentrated at the cell cortex/plasma membrane. |
| GO:0005737 cytoplasm | ISM GO_REF:0000122 | ACCEPT | Summary: Sequence-model prediction of cytoplasm. Reason: Consistent with experimental data. |
| GO:0005886 plasma membrane | IDA PMID:25843888 The BASL polarity protein controls a MAPK signaling feedback... | ACCEPT | Summary: Functional YDA-YFP localizes to the plasma membrane in epidermal cells. Reason: Direct imaging of a complementing fusion. Supporting Evidence: PMID:25843888 YDA-YFP rescued loss-of-function yda mutants and showed localization at the plasma membrane, broadly in the leaf epidermal cells |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping. Reason: Consistent with experimental data. |
| GO:0005938 cell cortex | IDA PMID:25843888 The BASL polarity protein controls a MAPK signaling feedback... | ACCEPT | Summary: YDA-YFP is polarized at the cell cortex in stomatal lineage cells with BASL. Reason: The BASL-dependent cortical polarization of YODA is a key feature of its function in asymmetric division. Supporting Evidence: PMID:25843888 Interestingly, YDA-YFP was found polarized at the cell cortex in stomatal lineage cells |
| GO:0005938 cell cortex | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to cell cortex. Reason: Consistent with experimental data. |
| GO:0010098 suspensor development | IMP PMID:14718171 A MAPKK kinase gene regulates extra-embryonic cell fate in A... | ACCEPT | Summary: yda loss-of-function impairs zygote elongation and suspensor fate; gain-of-function exaggerates suspensor growth. Reason: A principal developmental role of YODA, in which the MAPK cascade acts as a switch promoting extra-embryonic (suspensor) fate. Supporting Evidence: PMID:14718171 In loss-of-function mutants, the zygote does not elongate properly, and the cells of the basal lineage are eventually incorporated into the embryo instead of differentiating the extra-embryonic suspensor. |
| GO:0010103 stomatal complex morphogenesis | IMP PMID:15178800 Stomatal development and pattern controlled by a MAPKK kinas... | MODIFY | Summary: yda null mutants have excess stomata; constitutively active YDA eliminates stomata. Reason: The data show that YODA is a negative regulator of stomatal development (lineage entry and spacing) rather than a participant in stomatal morphogenesis; negative regulation of stomatal complex development is the accurate term. Proposed replacements: negative regulation of stomatal complex development Supporting Evidence: PMID:15178800 Null mutations in YODA lead to excess stomata, whereas constitutive activation of YODA eliminated stomata. |
| GO:0010229 inflorescence development | IMP PMID:23263767 A MAPK cascade downstream of ERECTA receptor-like protein ki... | KEEP AS NON CORE | Summary: YDA acts downstream of ERECTA and upstream of MKK4/5 in inflorescence architecture. Reason: Genuine developmental role of the ERECTA-YDA-MAPK module in localized cell proliferation; non-core relative to the MAPKKK activity itself. Supporting Evidence: PMID:23263767 YODA (YDA), a MAPKK kinase, was shown to be upstream of MKK4/MKK5 and downstream of ER in regulating inflorescence architecture |
| GO:0106310 protein serine kinase activity | EXP PMID:22307275 Brassinosteroid regulates stomatal development by GSK3-media... | ACCEPT | Summary: YDA phosphorylates MKK4 in vitro. Reason: Correct; the specific activity is MAP kinase kinase kinase activity. Supporting Evidence: PMID:22307275 BIN2 phosphorylates YDA to inhibit YDA phosphorylation of its substrate MKK4 |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based protein serine kinase activity. Reason: Correct, general. |
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Download this section (compressed HTML)Q: How is YODA activated by ERECTA-family receptors - is there a receptor-associated kinase (e.g. BSK/SSP-like) that relieves YODA N-terminal autoinhibition in the epidermis, as SSP does in the zygote?
Q: How is signalling specificity maintained when the same YDA-MKK4/5-MPK3/6 module controls stomatal fate, embryo patterning, inflorescence growth and immunity-related outputs?
Experiment: Identify YODA-activating partners in stomatal lineage cells by proximity labelling (TurboID-YDA) with and without EPF2 treatment, followed by genetic tests of candidate BSK-family kinases.
Type: proximity proteomics / genetics
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