Brassinosteroid Insensitive 2 (BIN2)

Brassinosteroid Insensitive 2 (BIN2) is a critical negative regulator of the brassinosteroid (BR) signaling pathway in Arabidopsis thaliana, functioning as a GSK3/shaggy-like serine/threonine protein kinase (UniProt P92939). In the absence of brassinosteroids, BIN2 phosphorylates the transcription factors BES1 and BZR1, which leads to their sequestration in the cytoplasm by 14-3-3 proteins and subsequent proteasomal degradation, effectively silencing BR-mediated growth responses (PubMed: 12019246). When BR levels are high, the BRI1 receptor complex triggers a signaling cascade that inhibits BIN2 activity, allowing dephosphorylated BES1/BZR1 to accumulate in the nucleus and activate gene expression. Beyond its role in growth, BIN2 is involved in various developmental processes including stomatal patterning and vascular differentiation, as well as responses to environmental stresses like salt and drought (PubMed: 25103419). Small molecule inhibitors such as Bikinin have been developed to specifically target BIN2 and its close homologs, providing tools to study plant development and potentially enhance crop yields by modulating BR sensitivity (PubMed: 19122107). Due to its high homology with human GSK3β, BIN2 also serves as a valuable model for studying kinase regulation and the development of therapeutic scaffolds for human diseases like Alzheimer's and type 2 diabetes.

Other names

GSK3-like kinase BIN2Shaggy-related protein kinase etaAtSK21UCW1SK21Arabidopsis thaliana BIN2

BIN2 acts as a negative regulator of the brassinosteroid pathway by phosphorylating transcription factors BES1 and BZR1, which leads to their cytoplasmic sequestration and proteasomal degradation. Inhibitors like Bikinin act as ATP-competitive antagonists to block BIN2 kinase activity, thereby activating the brassinosteroid response.