Disease relevance of BRI1

• Removal of BRI1's C terminus leads to a hypersensitive receptor, indicated by suppression of dwarfism of BR-deficient and BR-perception mutants and by enhanced BR signaling as a result of elevated phosphorylation of BRI1 [1].
• The bri1 mutant showed multiple deficiencies in developmental pathways that could not be rescued by brassinosteroid treatment including a severely dwarfed stature; dark green, thickened leaves; males sterility; reduced apical dominance; and de-etiolation of dark-grown seedlings [2].

High impact information on BRI1

• BRI1/BAK1, a receptor kinase pair mediating brassinosteroid signaling [3].
• We propose that BAK1 and BRI1 function together to mediate plant steroid signaling [3].
• BAK1 and BRI1 share similar gene expression and subcellular localization patterns and physically associate with each other in plants [3].
• In contrast, a bak1 knockout mutation gives rise to a weak bri1-like phenotype and enhances a weak bri1 mutation [3].
• Overexpression of the BAK1 gene leads to a phenotype reminiscent of BRI1-overexpression transgenic plants and rescues a weak bri1 mutant [3].

Biological context of BRI1

• The SERK1 mutant allele serk1-1 enhances the phenotype of the weak BRI1 allele bri1-119 [4].
• These findings support a role for TRIP-1 in the molecular mechanisms of BR-regulated plant growth and development, possibly as a cytoplasmic substrate of the BRI1 receptor kinase [5].
• Coexpression of BRI1 and AtSERK3 results in a change of the steady state distribution of both receptors because of accelerated endocytosis [6].
• In Arabidopsis thaliana brassinosteroid (BR), perception is mediated by two Leu-rich repeat receptor-like kinases, BRASSINOSTEROID INSENSITIVE1 (BRI1) and BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1) (Arabidopsis SOMATIC EMBRYOGENESIS RECEPTOR-like KINASE3 [AtSERK3]) [6].
• The extracellular leucine-rich repeat (LRR) and transmembrane domains of the Arabidopsis receptor kinase BRI1, which is implicated in brassinosteroid signaling, were fused to the serine/threonine kinase domain of XA21, the rice disease resistance receptor [7].

Anatomical context of BRI1

• TTL displays a similar expression pattern with BRI1 and is associated with the plasma membrane [8].
• Using transient expression in protoplasts of BRI1 and AtSERK3 fused to cyan and yellow fluorescent green fluorescent protein variants allowed us to localize each receptor independently in vivo [6].
• Endocytic vesicles contain either BRI1 or AtSERK3 alone or both [6].

Associations of BRI1 with chemical compounds

• BAK1 is a serine/threonine protein kinase, and BRI1 and BAK1 interact in vitro and in vivo [9].
• BRL1, a leucine-rich repeat receptor-like protein kinase, is functionally redundant with BRI1 in regulating Arabidopsis brassinosteroid signaling [10].
• Brassinosteroids (BRs) regulate multiple aspects of plant growth and development and require an active BRASSINOSTEROID-INSENSITIVE 1 (BRI1) receptor serine/threonine kinase for hormone perception and signal transduction [5].
• Site-directed mutagenesis of identified and predicted BRI1 phosphorylation sites revealed that the highly conserved activation loop residue T-1049 and either S-1044 or T-1045 were essential for kinase function in vitro and normal BRI1 signaling in planta [11].
• The full response to auxin, however, requires the functioning of BRI1 [12].

Physical interactions of BRI1

• TTL interacts with BRI1 in a kinase-dependent manner in yeast and is phosphorylated by BRI1 in vitro [8].
• Three clones, Y-1, 2 and 3, were found to interact commonly with the kinase domain of RLK902 and RKL1 and not to interact with the kinase domain of BRI1, a member of LRR-RLKs [13].

Enzymatic interactions of BRI1

• We now show that the BRI1 kinase domain phosphorylates Arabidopsis TRIP-1 on three specific sites in vitro (Thr-14, Thr-89 and either Thr-197 or Ser-198) [5].

Regulatory relationships of BRI1

• It is believed that BRI1 becomes activated through heterodimerization with BAK1, a similar LRR receptor kinase, in response to BR signal [8].
• Moreover, a weak response in the mutant suggests that DWF4 alone is likely to be regulated in other way(s) in addition to BRI1 mediation [14].

Other interactions of BRI1

• Using blue native gel electrophoresis, we show that SERK1 and SERK3 are part of BRI1-containing multiple protein complexes with relative masses between 300 and 500 kD [4].
• The Arabidopsis transthyretin-like protein is a potential substrate of BRASSINOSTEROID-INSENSITIVE 1 [8].
• Based on sequence similarity, we have identified three members of the BRI1 family, named BRL1, BRL2 and BRL3 [15].
• However, their response to fluctuation of BR levels was highly reduced (DWF4) or nullified (the other eight genes) in a bri1 mutant [14].
• It was proposed that BR signals, perceived by a membrane BR receptor complex that contains the leucine (Leu)-rich repeat receptor-like kinase BRI1, inactivate BIN2 to relieve its inhibitory effect on unknown downstream BR-signaling components [16].

Analytical, diagnostic and therapeutic context of BRI1

• Sequence alignment revealed that BRL1 is closely related to BRI1, which is involved in BR perception [10].
• Immunoprecipitation of epitope-tagged BRI1 from Arabidopsis thaliana followed by liquid chromatography-tandem mass spectrometry (LC/MS/MS) identified S-838, S-858, T-872, and T-880 in the juxtamembrane region, T-982 in the kinase domain, and S-1168 in C-terminal region as in vivo phosphorylation sites of BRI1 [11].
• Matrix-assisted laser desorption/ionization mass spectrometry identified a minimum of 12 sites of autophosphorylation in the cytoplasmic domain of BRI1, including five in the juxtamembrane region (N-terminal to the catalytic KD), five in the KD (one each in sub-domains I and VIa and three in sub-domain VIII), and two in the carboxy terminal region [17].
• Confocal microscopy analysis of full-length BRI1 fused to green fluorescent protein indicates that BRI1 is localized in the plasma membrane, and an in vitro kinase assay indicates that BRI1 is a functional Ser/Thr kinase [18].

References