Mastering the balance: BAK1’s dual roles in steering plant growth and immunity

Abstract

BAK1 was initially identified as a coreceptor of BRI1 in regulating the brassinosteroid-triggered signaling pathway in Arabidopsis. Over the past two decades, increasing pieces of evidence have demonstrated that BAK1 and its close paralogs form receptor-coreceptor complexes with distinct ligand-binding receptors. Through ligand-induced heterodimerization with receptor-like protein kinases or receptor-like proteins, BAK1 thereby regulates a variety of physiological events such as plant development, immunity, and stress responses. Thus, BAK1 plays a central role in directly governing the trade-offs of multiple signaling pathways. Deciphering the molecular mechanisms underlying how BAK1 coordinates plant growth and defense, with specific emphasis on its coreceptor functions, holds significant potential for future advancements in crop breeding. This review seeks to explore the latest insights into how BAK1 impacts the intricate equilibrium between plant development and immunity, as well as its roles in coordinating the activation of pattern-triggered immunity and effector-triggered immunity or programmed cell death. Furthermore, it offers significant perspectives on why BAK1 has been chosen as a shared component in determining plant growth and defense mechanisms across model plants to horticultural crops.

Acknowledgments

The authors thank Prof. Kai He from Lanzhou University, Prof. Jia Li from Guangzhou University, and Prof. Yu Yang from Shenzhen University for critical discussions. This work was supported by the National Natural Science Foundation of China (32360460 to W.W., 32200232 to Y.W.), National Science Foundation for Distinguished Young scholars of Qinghai Province (2024-ZJ-907 to Y.W.), National Science Foundation of Gansu Province (22JR5RA526 to Y.W., 23JRRA699 to W.W.), China Postdoctoral Science Foundation (2022M711450 to Y.W.), Science-Technology Foundation for Middle-aged and Young Scientist of Qinghai Normal University (2023QZR013 to Y.W.), and State Key Laboratory of Aridland Crop Science of Gansu Agricultural University (GSCS-2023-04 to W.W.).

Author contributions

Y.W. prepared the manuscript. W.W. revised the manuscript. W.W. provided assistance with the manuscript. Y.M. and S.Z. provided assistance with the figures. All authors read and approved the final manuscript.

Data availability

No datasets were generated or analyzed during the current study.

Conflict of interest statement

None declared.

References

[1] Hecht V, Vielle-Calzada JP, Hartog MV. et al. The Arabidop-sis Somatic Embryogenesis Receptor Kinase 1 gene is expressed in developing ovules and embryos and enhances embryogenic competence in culture. Plant Physiol. 2001; 127:803-16

[2] He K, Wu Y. Receptor-like kinases and regulation of plant innate immunity. Enzyme. 2016; 40:105-42

[3] He K, Xu S, Li J. BAK1 directly regulates brassinosteroid percep-tion and BRI1 activation. J Integr Plant Biol. 2013; 55:1264-70

[4] Wu D,LiuY,XuF. et al. Differential requirement of BAK1 C-terminal tail in development and immunity. J Integr Plant Biol. 2018; 60:270-5

[5] Li J, Wen J, Lease KA. et al. BAK1, an Arabidopsis LRR receptor-like protein kinase, interacts with BRI1 and modulates brassi-nosteroid signaling. Cell. 2002; 110:213-22

[6] Nam KH, Li J. BRI1/BAK1, a receptor kinase pair mediating brassinosteroid signaling. Cell. 2002; 110:203-12

[7] Gou X, Yin H, He K. et al. Genetic evidence for an indispensable role of somatic embryogenesis receptor kinases in brassinos-teroid signaling. PLoS Genet. 2012; 8:e1002452

[8] He K, Gou X, Yuan T. et al. BAK1 and BKK1 regulate brassinosteroid-dependent growth and brassinosteroid-independent cell-death pathways. Curr Biol. 2007; 17:1109-15

[9] Chinchilla D, Shan L, He P. et al. One for all: the receptor-associated kinase BAK1. Trends Plant Sci. 2009; 14:535-41

[10] Gou XP, Li J. Paired receptor and coreceptor kinases perceive extracellular signals to control plant development. Plant Physiol. 2020; 182:1667-81

[11] Gao X, Ruan X, Sun Y. et al. BAKing up to survive a battle: functional dynamics of BAK1 in plant programmed cell death. Front Plant Sci. 2018; 9:1913

[12] Yasuda S, Okada K, Saijo Y. A look at plant immunity through the window of the multitasking coreceptor BAK1. Curr Opin Plant Biol. 2017; 38:10-8

[13] Schmidt ED, Guzzo F, Toonen MA. et al. A leucine-rich repeat containing receptor-like kinase marks somatic plant cells com-petent to form embryos. Development. 1997; 124:2049-62

[14] Zhu JY, Sae-Seaw J, Wang ZY. Brassinosteroid signalling. Devel-opment. 2013; 140:1615-20

[15] Kemmerling B, Schwedt A, Rodriguez P. et al. The BRI1-associated kinase 1, BAK1, has a brassinolide-independent role in plant cell-death control. Curr Biol. 2007; 17:1116-22

[16] Chinchilla D, Zipfel C, Robatzek S. et al. A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature. 2007; 448:497-500

[17] Heese A, Hann DR, Gimenez-Ibanez S. et al. The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity in plants. Proc Natl Acad Sci U S A. 2007; 104:12217-22

[18] Ladwig F, Dahlke RI, Stührwohldt N. et al. Phytosulfokine reg-ulates growth in Arabidopsis through a response module at the plasma membrane that includes CYCLIC NUCLEOTIDE-GATED CHANNEL 17, H1-ATPase, and BAK1. Plant Cell. 2015; 27: 1718-29

[19] Ou Y, Lu X, Zi Q. et al. RGF 1 INSENSITIVE 1 to 5, a group of LRR receptor-like kinases, are essential for the perception of root meristem growth factor 1 in Arabidopsis thaliana. Cell Res. 2016; 26:686-98

[20] Zhang H, Lin X, Han Z. et al. SERK family receptor-like kinases function as co-receptors with PXY for plant vascular develop-ment. Mol Plant. 2016; 9:1406-14

[21] Meng X, Chen X, Mang H. et al. Differential function of Arabidopsis SERK family receptor-like kinases in stomatal patterning. Curr Biol. 2015; 25:2361-72

[22] Meng X, Zhou J, Tang J. et al. Ligand-induced receptor-like kinase complex regulates floral organ abscission in Arabidopsis. Cell Rep. 2016; 14:1330-8

[23] Jorda L, Sopena-Torres S, Escudero V. et al. ERECTA and BAK 1 receptor like kinases interact to regulate immune responses in Arabidopsis. Front Plant Sci. 2016; 7:897

[24] Qian P, Song W, Yokoo T. et al. The CLE9/10 secretory peptide regulates stomatal and vascular development through distinct receptors. Nat Plants. 2018; 4:1071-81

[25] Li M, Lv M, Wang X. et al. The EPFL-ERf-SERK signaling controls integument development in Arabidopsis. New Phytol. 2023; 238: 186-201

[26] Zhang H, Li X, Wang W. et al. SERKs regulate embryonic cuticle integrity through the TWS1-GSO1/2 signaling pathway in Ara-bidopsis. New Phytol. 2022; 233:313-28

[27] Zipfel C, Kunze G, Chinchilla D. et al. Perception of the bac-terial PAMP EF-Tu by the receptor EFR restricts Agrobacterium-mediated transformation. Cell. 2006; 125:749-60

[28] Hou S, Liu D, Huang S. et al. The Arabidopsis MIK2 receptor elicits immunity by sensing a conserved signature from phyto-cytokines and microbes. Nat Commun. 2021; 12:5494

[29] Rhodes J, Yang H, Moussu S. et al. Perception of a divergent family of phytocytokines by the Arabidopsis receptor kinase MIK2. Nat Commun. 2021; 12:705

[30] Krol E, Mentzel T, Chinchilla D. et al. Perception of the Arabidopsis danger signal peptide 1 involves the pattern recognition receptor AtPEPR1 and its close homologue AtPEPR2. JBiolChem. 2010; 285: 13471-9

[31] Albert I, Bohm H, Albert M. et al. An RLP23-SOBIR1-BAK 1 complex mediates NLP-triggered immunity. Nat Plants. 2015; 1: 15140

[32] Zhang W, Fraiture M, Kolb D. et al. Arabidopsis receptor-like pro-tein 30 and receptor-like kinase suppressor of BIR1-1 /EVERSHED mediate innate immunity to necrotrophic fungi. Plant Cell. 2013; 25:4227-41

[33] Postma J, Liebrand TW, Bi G. et al. Avr4 promotes Cf-4 receptor-like protein association with the BAK1/SERK3 receptor-like kinase to initiate receptor endocytosis and plant immunity. New Phytol. 2016; 210:627-42

[34] Saur IML, Kadota Y, Sklenar J. et al. NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in Nicotiana benthamiana. Proc Natl Acad Sci U S A. 2016; 113: 3389-94

[35] Zhao T, Ma S, Kong Z. et al. Recognition of the inducible, secretory small protein OsSSP1 by the membrane receptor OsSSR1 and the co-receptor OsBAK1 confers rice resistance to the blast fungus. Mol Plant. 2024; 17:807-23

[36] Sun Y, Li L, Macho AP. et al. Structural basis for flg22-induced activation of the Arabidopsis FLS2-BAK1 immune complex. Sci-ence. 2013; 342:624-8

[37] Sun Y, Han Z, Tang J. et al. Structure reveals that BAK1 as a co-receptor recognizes the BRI1-bound brassinolide. Cell Res. 2013; 23:1326-9

[38] Wei X, Liu X, Zhang X. et al. Structural insights into ligand recognition and receptor activation of plant leucine-rich repeat (LRR) transmembrane receptors. New Crops. 2024; 1:100022

[39] Schwessinger B, Roux M, Kadota Y. et al. Phosphorylation-dependent differential regulation of plant growth, cell death, and innate immunity by the regulatory receptor-like kinase BAK1. PLoS Genet. 2011; 7:e1002046

[40] Moffett AS, Shukla D. Structural consequences of multisite phosphorylation in the BAK1 kinase domain. Biophys J. 2020; 118: 698-707

[41] Yan L, Ma Y, Liu D. et al. Structural basis for the impact of phosphorylation on the activation of plant receptor-like kinase BAK1. Cell Res. 2012; 22:1304-8

[42] Wang X, Kota U, He K. et al. Sequential transphosphorylation of the BRI1/BAK1 receptor kinase complex impacts early events in brassinosteroid signaling. Dev Cell. 2008; 15:220-35

[43] Perraki A, DeFalco TA, Derbyshire P. et al. Phosphocode-dependent functional dichotomy of a common co-receptor in plant signalling. Nature. 2018; 561:248-52

[44] Segonzac C, Macho AP, Sanmartin M. et al. Negative control of BAK1 by protein phosphatase 2A during plant innate immunity. EMBO J. 2014; 33:2069-79

[45] Diao Z, Yang R, Wang Y. et al. Functional screening of the Arabidopsis 2C protein phosphatases family identifies PP2C15 as a negative regulator of plant immunity by targeting BRI1-associated receptor kinase 1. Mol Plant Pathol. 2024; 25:e13447

[46] Rhodes J, Roman AO, Bjornson M. et al. Perception of a conserved family of plant signalling peptides by the receptor kinase HSL3. Elife. 2022; 11:627-42

[47] Yamada K, Yamashita-Yamada M, Hirase T. et al. Danger peptide receptor signaling in plants ensures basal immunity upon pathogen-induced depletion of BAK1. EMBO J. 2016; 35: 46-61

[48] Gust AA, Felix G. Receptor like proteins associate with SOBIR1-type of adaptors to form bimolecular receptor kinases. Curr Opin Plant Biol. 2014; 21:104-11

[49] Liebrand TW, van den Burg HA, Joosten MH. Two for all: receptor-associated kinases SOBIR1 and BAK1. Trends Plant Sci. 2014; 19: 123-32

[50] Yang K, Wang Y, Li J. et al. The Pythium periplocum elicitin PpEli2 confers broad-spectrum disease resistance by triggering a novel receptor-dependent immune pathway in plants. Hortic Res. 2022;10:uhac255

[51] Campos MD, Félix MDR, Patanita M. et al. High throughput sequencing unravels tomato-pathogen interactions towards a sustainable plant breeding. Hortic Res. 2021; 8:171

[52] Han M, Wang C, Zhu W. et al. Extracellular perception of multiple novel core effectors from the broad host-range pear anthrac-nose pathogen Colletotrichum fructicola in the nonhost Nicotiana benthamiana. Hortic Res. 2024;11:uhae078

[53] Wu Y, Gao Y, Zhan Y. et al. Loss of the common immune coreceptor BAK1 leads to NLR-dependent cell death. Proc Natl Acad Sci U S A. 2020; 117:27044-53

[54] Schulze S, Yu L, Hua C. et al. The Arabidopsis TIR-NBS-LRR protein CSA1 guards BAK1-BIR3 homeostasis and mediates convergence of pattern-and effector-induced immune responses. Cell Host Microbe. 2022; 30:1717-1731.e6

[55] Yang Y, Kim NH, Cevik V. et al. Allelic variation in the Arabidopsis TNL CHS3/CSA1 immune receptor pair reveals two functional cell-death regulatory modes. Cell Host Microbe. 2022; 30:1701-1716.e5

[56] Yu X, Xie Y, Luo D. et al. A phospho-switch constrains BTL2-mediated phytocytokine signaling in plant immunity. Cell. 2023; 186:2329-2344.e20

[57] Halter T, Imkampe J, Mazzotta S. et al. The leucine-rich repeat receptor kinase BIR2 is a negative regulator of BAK1 in plant immunity. Curr Biol. 2014; 24:134-43

[58] Imkampe J, Halter T, Huang SH. et al. The Arabidopsis leucine-rich repeat receptor kinase BIR3 negatively regulates BAK1 recep-tor complex formation and stabilizes BAK1. Plant Cell. 2017; 29: 2285-303

[59] Li B, Ferreira MA, Huang ML. et al. The receptor-like kinase NIK1 targets FLS2/BAK1 immune complex and inversely mod-ulates antiviral and antibacterial immunity. Nat Commun. 2019; 10:4996

[60] Mang H, Feng B, Hu Z. et al. Differential regulation of two-tiered plant immunity and sexual reproduction by ANXUR receptor-like kinases. Plant Cell. 2017; 29:3140-56

[61] Yeh YH, Panzeri D, Kadota Y. et al. The Arabidopsis malectin-like/LRR-RLK IOS1 is critical for BAK1-dependent and BAK1-independent pattern-triggered immunity. Plant Cell. 2016; 28: 1701-21

[62] Ma Q, Hu Z, Mao Z. et al. A novel leucine-rich repeat receptor-like kinase MRK1 regulates resistance to multiple stresses in tomato. Hortic Res. 2022;9:uhab088

[63] Stegmann M, Monaghan J, Smakowska-Luzan E. et al. The recep-tor kinase FER is a RALF-regulated scaffold controlling plant immune signaling. Science. 2017; 355:287-9

[64] Mathieu J, Schwizer S, Martin GB. Pto kinase binds two domains of AvrPtoB and its proximity to the effector E3 ligase determines if it evades degradation and activates plant immunity. PLoS Pathog. 2014; 10:e1004227

[65] Wu AJ, Andriotis VM, Durrant MC. et al. A patch of surface-exposed residues mediates negative regulation of immune sig-naling by tomato Pto kinase. Plant Cell. 2004; 16:2809-21

[66] Cheng W, Munkvold KR, Gao HS. et al. Structural analysis of Pseudomonas syringae AvrPtoB bound to host BAK1 reveals two similar kinase-interacting domains in a type III effector. Cell Host Microbe. 2011; 10:616-26

[67] Janjusevic R, Abramovitch RB, Martin GB. et al.A bacterial inhibitor of host programmed cell death defenses is an E 3 ubiquitin ligase. Science. 2006; 311:222-6

[68] Zhou J, Wu S, Chen X. et al. The Pseudomonas syringae effector HopF2 suppresses Arabidopsis immunity by targeting BAK1. Plant J. 2014; 77:235-45

[69] Yamaguchi K, Nakamura Y, Ishikawa K. et al. Suppression of rice immunity by Xanthomonas oryzae type III effector Xoo2875. Biosci Biotechnol Biochem. 2013; 77:796-801

[70] Li L, Kim P, Yu L. et al. Activation-dependent destruction of a co-receptor by a Pseudomonas syringae effector dampens plant immunity. Cell Host Microbe. 2016; 20:504-14

[71] Yoshino K, Irieda H, Sugimoto F. et al. Cell death of Nicotiana benthamiana is induced by secreted protein NIS1 of Colletotrichum orbiculare and is suppressed by a homologue of CgDN3. Mol Plant Microbe Interact. 2012; 25:625-36

[72] Han R, Zhu T, Kong Z. et al. Understanding and manipulating the recognition of necrosis-inducing secreted protein 1 (NIS1) by BRI1-associated receptor kinase 1 (BAK1). Int J Biol Macromol. 2024; 278:134821

[73] Zhang S, Wang L, Jiang H. et al. Aconserved Phytophthora apoplas-tic trypsin-like serine protease targets the receptor-like kinase BAK1 to dampen plant immunity. Nat Plants. 2025; 11:1401-15

[74] Zhou J, Wang P, Claus LAN. et al. Proteolytic processing of SERK3/BAK1 regulates plant immunity, development, and cell death. Plant Physiol. 2019; 180:543-58

[75] Yu X, Xu GY, Li B. et al. The receptor kinases BAK1/SERK4 regulate Ca2+ channel-mediated cellular homeostasis for cell death containment. Curr Biol. 2019; 29:3778-3790.e8

[76] Bi GZ, Su M, Li N. et al. The ZAR1 resistosome is a calcium-permeable channel triggering plant immune signaling. Cell. 2021; 184:3528-3541.e12

[77] Jacob P, Kim NH, Wu F. et al. Plant "helper" immune receptors are Ca2+-permeable nonselective cation channels. Science. 2021; 373: 420-5

[78] Zhang Z, Wang Q, Yan H. et al. Lighting-up wars: stories of Ca2+ signaling in plant immunity. New Crops. 2024; 1:100027

[79] Gao M, Wang X, Wang D. et al. Regulation of cell death and innate immunity by two receptor-like kinases in Arabidopsis. Cell Host Microbe. 2009; 6:34-44

[80] Liu Y, Huang X, Li M. et al. Loss-of-function of Arabidop-sis receptor-like kinase BIR1 activates cell death and defense responses mediated by BAK1 and SOBIR1. New Phytol. 2016; 212: 637-45

[81] Domínguez-Ferreras A, Kiss-Papp M, Jehle AK. et al. An overdose of the Arabidopsis coreceptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1 or its ectodomain causes autoimmunity in a SUPPRESSOR OF BIR1-1-dependent manner. Plant Physiol. 2015; 168:1106-21

[82] Kim SY, Shang Y, Joo SH. et al. Overexpression of BAK1 causes salicylic acid accumulation and deregulation of cell death con-trol genes. Biochem Biophys Res Commun. 2017; 484:781-6

[83] Li D, Wang L, Wang M. et al. Engineering OsBAK1 gene as a molecular tool to improve rice architecture for high yield. Plant Biotechnol J. 2009; 7:791-806

[84] Khew CY, Teo CJ, Chan WS. et al. Brassinosteroid insensitive 1-associated kinase 1 (OsI-BAK1) is associated with grain filling and leaf development in rice. J Plant Physiol. 2015; 182:23-32

[85] Cao H, Yang Z, Song S. et al. Transcriptome analysis reveals genes potentially related to maize resistance to Rhizoctonia solani. Plant Physiol Biochem. 2022; 193:78-89

[86] Smith JM, Salamango DJ, Leslie ME. et al. Sensitivity to Flg22 is modulated by ligand-induced degradation and de novo synthe-sis of the endogenous flagellin-receptor FLAGELLIN-SENSING2. Plant Physiol. 2014; 164:440-54

[87] Lu D, Lin W, Gao X. et al. Direct ubiquitination of pattern recog-nition receptor FLS2 attenuates plant innate immunity. Science. 2011; 332:1439-42

[88] Song L, Shi QM, Yang XH. et al. Membrane steroid-binding pro-tein 1 (MSBP1) negatively regulates brassinosteroid signaling by enhancing the endocytosis of BAK1. Cell Res. 2009; 19:864-76

[89] Xia S, Han D, Mo Q. et al. SUMOylation of BAK1 regulates its co-receptor function for specifically activating brassinosteroid response. Plant Commun. 2025; 22:101384

[90] Bowman JL, Floyd SK, Sakakibara K. Green genes—comparative genomics of the green branch of life. Cell. 2007; 129:229-34

[91] Aan den Toorn M, Albrecht C, de Vries S. On the origin of SERKs: bioinformatics analysis of the somatic embryogenesis receptor kinases. Mol Plant. 2015; 8:762-82

[92] Jumper J, Evans R, Pritzel A. et al. Highly accurate protein struc-ture prediction with AlphaFold. Nature. 2021; 596:583-9