CBL4 (CALCINEURIN B-LIKE PROTEIN 4), also known as SOS3 (SALT OVERLY SENSITIVE 3), is a small (222 aa) EF-hand calcium sensor of the plant calcineurin B-like (CBL) family that decodes salt-induced cytosolic Ca2+ signals. It is N-myristoylated at Gly-2 and S-acylated at Cys-3, which anchor it to the cytoplasmic face of the plasma membrane. Its EF hands bind Ca2+ (and Mn2+) with unusually low affinity, and Ca2+ binding drives dimerization and a conformational change. Ca2+-loaded CBL4 binds the C-terminal NAF/FISL motif of CBL-interacting protein kinases (CIPKs), relieving autoinhibition and activating the kinase. Its principal partner is CIPK24/SOS2: the CBL4-CIPK24 complex is recruited to the plasma membrane by CBL4, where CIPK24 phosphorylates the autoinhibitory C-terminus of the Na+/H+ antiporter SOS1, increasing Na+ extrusion. This SOS3-SOS2-SOS1 relay acts mainly in roots and is required for intracellular Na+/K+ homeostasis and tolerance to high NaCl; sos3 loss-of-function plants are salt hypersensitive, fail to grow on low K+, and are partly rescued by high external Ca2+. With CIPK6, CBL4 also promotes Ca2+-dependent translocation of the K+ channel AKT2 from the endoplasmic reticulum to the plasma membrane by a phosphorylation-independent mechanism that requires both of its lipid modifications. Despite its name and sequence similarity to calcineurin B, plants lack a calcineurin A catalytic subunit and CBL4 has no phosphatase partner; it signals through CIPK kinases instead.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004723 calcium-dependent protein serine/threonine phosphatase activity | ISS PMID:9632394 A calcium sensor homolog required for plant salt tolerance. | REMOVE | Summary: Sequence-similarity transfer from the yeast calcineurin B regulatory subunit made when SOS3 was cloned. CBL4 is a small non-catalytic EF-hand protein with no phosphatase domain, and the identified effector is a protein kinase, not a phosphatase. Reason: Even in fungi and animals the calcium-dependent phosphatase activity belongs to the catalytic calcineurin A subunit, not to the regulatory B subunit, so the transfer is wrong even for an orthologous calcineurin B. In addition, plants have no calcineurin A homolog and no phosphatase partner of SOS3 has been found; SOS3 instead binds and activates the SOS2/CIPK24 kinase (PMID:10725350). The real activity is captured by protein serine/threonine kinase activator activity (GO:0043539) elsewhere in this review. Supporting Evidence: PMID:10725350 However, as yet, no protein phosphatase has been found to interact with SOS3. Instead, SOS3 was found to interact with and activate a protein kinase encoded by SOS2. PMID:10725350 no genes similar to CNA have been identified from plants, yet file:ARATH/CBL4/CBL4-uniprot.txt Binding of a CBL protein to the regulatory NAF domain of a CIPK serine-threonine protein kinase lead to the activation of the kinase in a calcium-dependent manner. |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: Calcium binding by the EF-hand domains, inherited across the CBL clade. Directly demonstrated for CBL4 by 45Ca2+ overlay and by crystal structures of Ca2+-bound SOS3. Reason: Calcium binding is the sensing step of CBL4 function and is experimentally established for this protein; the sos3-1 EF-hand deletion that reduces Ca2+ binding abolishes SOS2 interaction and salt tolerance. Supporting Evidence: PMID:11006339 45 Ca 2+ overlay assays showed that the protein is capable of binding calcium PMID:15644219 We report the crystal structure of a dimeric SOS3 protein in complex with calcium, and with calcium and manganese. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro EF-hand domain mapping to calcium ion binding; consistent with experimental data for CBL4. Reason: The EF-hand mapping is correct for CBL4, which binds Ca2+ experimentally (PMID:11006339) and structurally (PMID:15644219). Supporting Evidence: PMID:11006339 45 Ca 2+ overlay assays showed that the protein is capable of binding calcium |
| GO:0005509 calcium ion binding | ISS PMID:11230129 The NAF domain defines a novel protein-protein interaction m... | ACCEPT | Summary: ISS calcium binding attributed to the NAF-domain paper, which describes CBL proteins as calcium sensors that bind CIPKs in a calcium-dependent manner. Reason: Consistent with direct experimental and structural evidence that CBL4 binds Ca2+. Supporting Evidence: PMID:11230129 The Arabidopsis calcineurin B-like calcium sensor proteins (AtCBLs) interact with a group of serine-threonine protein kinases (AtCIPKs) in a calcium-dependent manner. PMID:11006339 45 Ca 2+ overlay assays showed that the protein is capable of binding calcium |
| GO:0005513 detection of calcium ion | IBA GO_REF:0000033 | ACCEPT | Summary: CBL4 receives the salt-induced Ca2+ stimulus through its EF hands and converts it into a molecular signal (CIPK24 binding and activation). The target's own experimental annotation is among the IBA sources, which is expected for a well-characterized clade member. Reason: CBL4 is the Ca2+-sensing component of the SOS pathway and performs the detection step itself; Ca2+ binding is required for SOS2 interaction and activation. Supporting Evidence: PMID:15644219 This leads to a change in the global shape and surface properties of the protein that may be sufficient to transmit the Ca(2+) signal elicited during salt stress. PMID:11006339 The resulting mutant SOS3 protein was not able to interact with the SOS2 protein kinase and was less capable of activating it. |
| GO:0005513 detection of calcium ion | IMP PMID:9405721 An Arabidopsis mutant that requires increased calcium for po... | ACCEPT | Summary: The sos3 mutant was the first plant mutant with an altered Ca2+ response; its growth defects on low K+ and NaCl are suppressed by raised external Ca2+, consistent with a defective Ca2+ sensor. Reason: The phenotype alone shows an altered Ca2+ response; combined with the later molecular evidence that SOS3 is the EF-hand Ca2+ sensor of the pathway, the annotation is sound and consistent with the IBA row. Supporting Evidence: PMID:9405721 In addition to defining the first plant mutant with an altered calcium response PMID:9405721 Surprisingly, increased extracellular Ca2+ suppresses the growth defect of sos3 plants on low K+ or 50 mM NaCl. |
| GO:0005515 protein binding | IPI PMID:10590166 Novel protein kinases associated with calcineurin B-like cal... | MODIFY | Summary: Yeast two-hybrid interaction of CBL4 with CIPK1 (Q8RWC9), from the paper that defined the CIPK family as CBL partners. Reason: Bare protein binding is uninformative. The partner is a CIPK protein kinase and binding occurs through the kinase's CBL-interaction region, so protein kinase binding is the supported, more informative term. Activation of CIPK1 by CBL4 has not been shown, so the activator term is not proposed for this partner. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:10590166 In addition to a typical protein kinase domain, they all contain a unique C-terminal region that is both required and sufficient for interaction with the AtCBL-type but not calmodulin-type Ca(2)+ binding proteins from plants. |
| GO:0005515 protein binding | IPI PMID:10725350 The Arabidopsis SOS2 protein kinase physically interacts wit... | MODIFY | Summary: SOS3 binds the C-terminal regulatory domain of SOS2/CIPK24 (yeast two-hybrid and in vitro binding) and activates its kinase activity in a Ca2+-dependent manner. Reason: Bare protein binding is uninformative; the same paper shows the functional consequence of the interaction, activation of a Ser/Thr protein kinase, which is the core molecular function of CBL4. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: PMID:10725350 SOS3 activates SOS2 protein kinase activity in a Ca 2+ -dependent manner |
| GO:0005515 protein binding | IPI PMID:11006339 SOS3 function in plant salt tolerance requires N-myristoylat... | MODIFY | Summary: SOS3-SOS2 interaction; the Ca2+-binding-defective sos3-1 protein fails to bind SOS2 and is less able to activate it. Reason: Bare protein binding is uninformative; the paper ties the interaction to SOS2 kinase activation, so protein serine/threonine kinase activator activity is the informative term. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: PMID:11006339 The resulting mutant SOS3 protein was not able to interact with the SOS2 protein kinase and was less capable of activating it. |
| GO:0005515 protein binding | IPI PMID:11115898 Interaction specificity of Arabidopsis calcineurin B-like ca... | MODIFY | Summary: Yeast two-hybrid specificity screen of CBLs against CIPKs, including CBL4 with CIPK1. Reason: Bare protein binding is uninformative; the partner is a CIPK protein kinase, so protein kinase binding is the supported term. No activation of CIPK1 by CBL4 is reported. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:11115898 each individual member of AtCBL family specifically interacts with a subset of CIPKs |
| GO:0005515 protein binding | IPI PMID:11230129 The NAF domain defines a novel protein-protein interaction m... | MODIFY | Summary: CBL4-CIPK1 interaction mapped to the 24-residue NAF domain of the kinase. Reason: Bare protein binding is uninformative; the partner is a CIPK protein kinase bound through its NAF domain, so protein kinase binding is the supported term. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:11230129 Here we identify a 24 amino acid domain (NAF domain) unique to these kinases as being required and sufficient for interaction with all known AtCBLs. |
| GO:0005515 protein binding | IPI PMID:11402167 Molecular characterization of functional domains in the prot... | MODIFY | Summary: SOS3 binds the 21-residue FISL/NAF motif of SOS2, which is also the kinase autoinhibitory domain. Reason: Bare protein binding is uninformative; binding to the autoinhibitory motif is how SOS3 activates SOS2, and the paper states that SOS2 activity depends on SOS3 and calcium. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: PMID:11402167 Removal of the regulatory domain of SOS2, including the SOS3 binding motif, resulted in constitutive activation of the protein kinase, indicating that the SOS3 binding motif can serve as a kinase autoinhibitory domain PMID:11402167 SOS2 kinase activity is dependent on SOS3 and calcium |
| GO:0005515 protein binding | IPI PMID:17449811 SCABP8/CBL10, a putative calcium sensor, interacts with the ... | MODIFY | Summary: SOS3-SOS2 interaction used as a comparator in the paper characterizing the paralog SCaBP8/CBL10 (abstract-only in cache). Reason: Bare protein binding is uninformative. The SOS3-SOS2 interaction is the activating interaction of the SOS pathway, as stated in this paper's own summary, so the informative term is protein serine/threonine kinase activator activity. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: PMID:17449811 Under salt stress, the calcium sensor SOS3 activates the kinase SOS2 that positively regulates SOS1, a plasma membrane sodium/proton antiporter. |
| GO:0005515 protein binding | IPI PMID:17785451 Interaction of SOS2 with nucleoside diphosphate kinase 2 and... | REMOVE | Summary: SOS3-SOS2 interaction reported in a study of SOS2 partners NDPK2 and catalases, where SOS3 and NDPK2 bind the same SOS2 domain. Reason: Bare protein binding is uninformative, and this paper does not assay the functional consequence of SOS3 binding. The activating SOS3-SOS2 interaction is captured by GO:0043539 from other papers. Removal does not dispute the interaction. Supporting Evidence: PMID:17785451 SOS3 and NDPK2, as well as other SOS3-related SCaBPs ( 21 ), can interact with the same domain present in SOS2 and related SnRK3 kinases |
| GO:0005515 protein binding | IPI PMID:21262798 Activation of the plasma membrane Na/H antiporter Salt-Overl... | MODIFY | Summary: SOS2-SOS3 complex used to phosphorylate and activate SOS1 by relieving its C-terminal autoinhibition. Reason: Bare protein binding is uninformative; the paper uses SOS3 as the calcium-dependent activating subunit of the SOS2-SOS3 kinase complex, so protein serine/threonine kinase activator activity is the informative term. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: PMID:21262798 The SOS2–SOS3 calcium-dependent protein kinase complex up-regulates SOS1 activity |
| GO:0005515 protein binding | IPI PMID:26315018 ABC transporter PEN3/PDR8/ABCG36 interacts with calmodulin t... | REMOVE | Summary: Binding of CBL4 to the N-terminal cytoplasmic domain of the ABC transporter PEN3/ABCG36, detected on a protein microarray (AtPMA-5000) probed with PEN3; the paper follows up calmodulin CaM7, not CBL4. Reason: Bare protein binding is uninformative, and this in vitro array hit was not followed up for CBL4, so no more specific function can be assigned. Removal does not dispute the interaction. Supporting Evidence: PMID:26315018 Several of the proteins identified to interact with PEN3 in vitro represent cellular Ca(2+) sensors |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization mapped from the UniProt subcellular location, which derives from a fluorescent-protein localization survey of all ten Arabidopsis CBLs. Reason: A nuclear pool was observed experimentally (PMID:19832944), but CBL4 function depends on its lipid anchors and plasma-membrane recruitment of CIPKs. No nuclear function of CBL4 is known, and a small soluble fusion protein can diffuse into the nucleus. Supporting Evidence: file:ARATH/CBL4/CBL4-uniprot.txt Nucleus {ECO:0000269|PubMed:19832944} PMID:19832944 individual CBL proteins decode calcium signals not only at the plasma membrane and the tonoplast, but also in the cytoplasm and nucleus |
| GO:0005737 cytoplasm | IDA PMID:19686372 A genome-wide functional characterization of Arabidopsis reg... | KEEP AS NON CORE | Summary: Cytoplasmic localization from a GFP-fusion survey of pollen-expressed Ca2+ sensors in tobacco pollen tubes (abstract-only in cache; abstract names CBL2 and CBL3 results only). Reason: CBL4 is a peripheral protein on the cytoplasmic face of the plasma membrane and a cytoplasmic pool is also reported by UniProt from an independent study, so the annotation is plausible. The full text was not available to check the CBL4 result, so the curator's call is kept, but the functional location is the plasma membrane. Supporting Evidence: file:ARATH/CBL4/CBL4-uniprot.txt Cytoplasm {ECO:0000269|PubMed:19832944} |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasm mapped from the UniProt subcellular location (experimental, PMID:19832944). Reason: Correct but peripheral; the functional site of CBL4 is the cytoplasmic face of the plasma membrane. Supporting Evidence: file:ARATH/CBL4/CBL4-uniprot.txt Cytoplasm {ECO:0000269|PubMed:19832944} |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane as the site of activity, inherited across lipid-anchored CBLs (CBL1, CBL9 and others). CBL4 recruits SOS2/CIPK24 to the plasma membrane, where the complex activates SOS1. Reason: CBL4 is myristoylated and S-acylated, localizes to the plasma membrane, and recruits its kinase partner there; this is the core functional location. Supporting Evidence: PMID:12070350 SOS3 is essential for both the kinase activity of SOS2 and its recruitment to the plasma membrane. file:ARATH/CBL4/CBL4-uniprot.txt Cell membrane {ECO:0000269|PubMed:19832944} |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane mapped from the UniProt subcellular location (cell membrane, lipid anchor; experimental). Reason: Core functional location, consistent with the IBA row and experimental data. Supporting Evidence: file:ARATH/CBL4/CBL4-uniprot.txt Note=The cell membrane localization is S-acylation dependent. |
| GO:0005886 plasma membrane | ISM GO_REF:0000122 | ACCEPT | Summary: AtSubP sequence-based prediction of plasma membrane localization. Reason: The prediction agrees with experimental localization and with the plasma-membrane recruitment of SOS2 by SOS3. Supporting Evidence: PMID:12070350 SOS3 is essential for both the kinase activity of SOS2 and its recruitment to the plasma membrane. |
| GO:0005955 calcineurin complex | ISS PMID:9632394 A calcium sensor homolog required for plant salt tolerance. | REMOVE | Summary: Transferred from yeast calcineurin B at cloning, on the hypothesis that SOS3 acts through a calcineurin-like phosphatase. Reason: The calcineurin complex is a calcineurin A/B phosphatase heterodimer. Plants have no calcineurin A, and no phosphatase partner of SOS3 has been found; CBL4 instead forms complexes with CIPK protein kinases (SOS2/CIPK24, CIPK6). The hypothesis behind this ISS was overturned by the identification of SOS2 as the SOS3 effector. Supporting Evidence: PMID:10725350 However, as yet, no protein phosphatase has been found to interact with SOS3. Instead, SOS3 was found to interact with and activate a protein kinase encoded by SOS2. PMID:10725350 Our results imply that plant salt tolerance may be mediated not by a calcineurin-like protein phosphatase but, rather, by the SOS3/SOS2 kinase complex. |
| GO:0019722 calcium-mediated signaling | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro CBL family (CNBL1-10) mapping to calcium-mediated signaling. CBL4 relays the salt-induced Ca2+ signal to CIPK24. Reason: CBL4 is a Ca2+ sensor that transmits the signal by activating CIPK kinases in a Ca2+-dependent manner; this is a core process. Supporting Evidence: PMID:10725350 SOS3 activates SOS2 protein kinase activity in a Ca 2+ -dependent manner PMID:17499048 The plant SOS2 family of protein kinases and their interacting activators, the SOS3 family of calcium-binding proteins, function together in decoding calcium signals elicited by different environmental stimuli. |
| GO:0019900 kinase binding | IEA GO_REF:0000002 | MODIFY | Summary: InterPro CBL family mapping to kinase binding. True (CBL4 binds the NAF domain of CIPKs) but more general than the supported activity. Reason: The binding is to Ser/Thr protein kinases of the CIPK family and activates them; the more specific supported term is protein serine/threonine kinase activator activity, which this review proposes from several IPI rows. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: file:ARATH/CBL4/CBL4-uniprot.txt Binding of a CBL protein to the regulatory NAF domain of a CIPK serine-threonine protein kinase lead to the activation of the kinase in a calcium-dependent manner. |
| GO:0030007 intracellular potassium ion homeostasis | IMP PMID:9405721 An Arabidopsis mutant that requires increased calcium for po... | KEEP AS NON CORE | Summary: sos3 seedlings cannot grow on low K+ and accumulate less K+ and more Na+ under NaCl stress. CBL4 also acts with CIPK6 to target the K+ channel AKT2 to the plasma membrane. Reason: The phenotype is well supported, but the K+ defect is largely secondary to Na+ toxicity under salt stress (SOS1 itself shows no K+ transport), and the AKT2 branch is a separate, developmental role. Retained as a genuine but non-core process. Supporting Evidence: PMID:9405721 Under NaCl stress, sos3 seedlings accumulated more Na+ and less K+ than the wild type. PMID:10725350 The Arabidopsis thaliana SOS2 and SOS3 genes are required for intracellular Na + and K + homeostasis |
| GO:0042538 hyperosmotic salinity response | IBA GO_REF:0000033 | ACCEPT | Summary: Response to increased salt, inherited from the CBL clade (CBL10/SCaBP8 donor). CBL4/SOS3 is the founding salt-tolerance CBL; sos3 mutants are hypersensitive to NaCl. Reason: Correct and core; CBL4 acts in the Ca2+-dependent SOS pathway that mediates the root response to high NaCl. Supporting Evidence: PMID:9632394 A mutation in the SOS3 gene renders Arabidopsis thaliana plants hypersensitive to Na+-induced growth inhibition. PMID:17449811 We show that SOS3 acts primarily in roots under salt stress. |
| GO:0042539 hypotonic salinity response | IMP PMID:9405721 An Arabidopsis mutant that requires increased calcium for po... | MODIFY | Summary: The cited phenotype is hypersensitivity of sos3 to high Na+ and Li+, i.e. to increased salt concentration. GO:0042539 is defined as a response to a decrease in salt concentration. Reason: The direction of the term is wrong for the evidence. The paper assays growth on added NaCl and LiCl, matching GO:0042538 hyperosmotic salinity response (response to an increase in salt concentration), which the gene already carries by IBA. Proposed replacements: hyperosmotic salinity response Supporting Evidence: PMID:9405721 which is hypersensitive to Na+ and Li+ stresses |
| GO:0071472 cellular response to salt stress | IMP PMID:36834961 Salinity-Induced Cytosolic Alkaline Shifts in Arabidopsis Ro... | ACCEPT | Summary: Salinity-induced cytosolic alkalinization in root cells is largely lost in the sos3-1 mutant, showing that the cellular response to NaCl requires SOS3. Reason: Direct cellular-level evidence that CBL4/SOS3 is required for the cellular response to salt stress, consistent with its role in activating the SOS2-SOS1 Na+/H+ exchange relay. Supporting Evidence: PMID:36834961 These pHcyt changes were substantially reduced in mutant roots lacking a functional SOS3/CBL4 protein |
| GO:0006883 intracellular sodium ion homeostasis | IMP PMID:9405721 An Arabidopsis mutant that requires increased calcium for po... | NEW | Summary: Proposed annotation. sos3 seedlings accumulate excess Na+ under salt stress, and SOS3 is the Ca2+-sensing subunit of the SOS2-SOS3 kinase complex that activates the plasma-membrane Na+/H+ exchanger SOS1. Reason: CBL4 does part of the work of the pathway, not merely being required for it. It senses the Ca2+ signal, activates CIPK24, and recruits it to the plasma membrane next to SOS1; a constitutively active SOS2 cannot fully replace the SOS2/SOS3 complex in vivo. Plasma-membrane Na+/H+ exchange is reduced in sos3 vesicles. The existing IMP row from the same paper already covers K+ homeostasis but not the primary Na+ defect. This matches the module-level process of the SOS pathway and the NEW row proposed for CIPK24. Supporting Evidence: PMID:9405721 Under NaCl stress, sos3 seedlings accumulated more Na+ and less K+ than the wild type. PMID:12034882 These results demonstrate that SOS1 contributes to plasma membrane Na(+)/H(+) exchange and that SOS2 and SOS3 regulate SOS1 transport activity. PMID:12070350 We propose a model in which SOS3 activates and directs SOS2 to the plasma membrane for the stimulatory phosphorylation of the Na+ transporter SOS1. |
| GO:0043495 protein-membrane adaptor activity | IDA PMID:12070350 Reconstitution in yeast of the Arabidopsis SOS signaling pat... | NEW | Summary: Proposed annotation. In the yeast SOS Recruitment System, SOS3 brings SOS2 to the plasma membrane. Recruitment is a separate essential contribution of SOS3, because a hyperactive, SOS3-independent SOS2 cannot fully replace the SOS2/SOS3 complex for SOS1 activation in vivo. Reason: CBL4 carries the membrane anchor (N-myristoylation at Gly-2 and S-acylation at Cys-3) for the CBL-CIPK complex, which matches the definition of bringing a protein or complex to a membrane. The same lipid-anchor-dependent mechanism moves the CIPK6-AKT2 complex to the plasma membrane (PMID:21445098). Kinase activation (GO:0043539) does not capture this second activity. Supporting Evidence: PMID:12070350 SOS3 is essential for both the kinase activity of SOS2 and its recruitment to the plasma membrane. file:ARATH/CBL4/CBL4-uniprot.txt The N-terminal 18 amino acids are sufficient for the cell membrane targeting of a heterologous protein. |
| GO:0072659 protein localization to plasma membrane | IDA PMID:21445098 Calcium-dependent modulation and plasma membrane targeting o... | NEW | Summary: Proposed annotation. CBL4, through its myristoyl and palmitoyl anchors, brings its CIPK partners to the plasma membrane. It recruits SOS2/CIPK24 there in a yeast reconstitution, and with CIPK6 it drives Ca2+-dependent translocation of the AKT2 K+ channel from the ER to the plasma membrane in plant cells. Reason: CBL4 performs the targeting step itself. Its dual lipid modification provides the membrane-targeting signal, and the AKT2 translocation is kinase-interaction-dependent but phosphorylation-independent, so the effect is not just a downstream result of kinase activation. No existing row captures this experimentally established role. Supporting Evidence: PMID:21445098 the isolated regulatory C-terminal domain of CIPK6 is sufficient for mediating CBL4- and Ca(2+)-dependent channel translocation from the endoplasmic reticulum membrane to the PM by a novel targeting pathway that is dependent on dual lipid modifications of CBL4 by myristoylation and palmitoylation PMID:12070350 SOS3 is essential for both the kinase activity of SOS2 and its recruitment to the plasma membrane. |
Loading supporting content…
Download this section (compressed HTML)Q: Is CBL4 the only Ca2+ sensor needed to activate CIPK24 in the root epidermis and the sodium-sensing niche, or do CBL8 and CBL10 share this role in particular root cell types?
Q: Do the weak CBL4 interactions with CIPK1, CIPK10, CIPK11 and CIPK15 seen in yeast two-hybrid assays have physiological roles in planta?
Q: The TAIR ISS annotations to calcium-dependent protein serine/threonine phosphatase activity and to calcineurin complex (PMID:9632394) and the IMP annotation to hypotonic salinity response (PMID:9405721) look like legacy or direction errors. Should they be retired or corrected to hyperosmotic salinity response?
Experiment: Cell-type-specific complementation of sos3 (for example epidermis vs stele promoters) combined with Ca2+ and pH imaging, to map where CBL4-dependent CIPK24 activation is needed for root salt tolerance.
Experiment: Test whether the low-affinity EF hands of CBL4 set the Ca2+ threshold for SOS pathway activation, by engineering higher-affinity EF-hand variants and measuring CIPK24 activation, SOS1 phosphorylation and salt tolerance in planta.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)