CBL–CIPK module-mediated phosphoregulation: facts and hypothesis

Abstract

Calcium (Ca2+) signaling is a versatile signaling network in plant and employs very efficient signal decoders to transduce the encoded message. The CBL–CIPK module is one of the sensor-relay decoders that have probably evolved with the acclimatization of land plant. The CBLs are unique proteins with non-canonical Ca2+ sensing EF-hands, N-terminal localization motif and a C-terminal phosphorylation motif. The partner CIPKs are Ser/Thr kinases with kinase and regulatory domains. Phosphorylation plays a major role in the functioning of the module. As the module has a functional kinase to transduce signal, it employs phosphorylation as a preferred mode for modulation of targets as well as its interaction with CBL. We analyze the data on the substrate regulation by the module from the perspective of substrate phosphorylation. We have also predicted some of the probable sites in the identified substrates that may be the target of the CIPK mediated phosphorylation. In addition, phosphatases have been implicated in reversing the CIPK mediated phosphorylation of substrates. Therefore, we have also presented the role of phosphatases in the modulation of the CBL–CIPK and its targets. We present here an overview of the phosphoregulation mechanism of the CBL–CIPK module.

The CBL–CIPK Pathway in Plant Response to Stress Signals

“…Remarkably, phosphorylation is the main mechanism coordinating the effects of CBL-CIPK on downstream proteins. Phosphorylation sites have been gradually identified in the CBL-CIPK pathway [25]. (We describe the detailed consequences of these findings in the section titled Functions of the CBL-CIPK Pathway.…”

“…Then, AtCIPK23, which is encoded by the LKS1 (low-K + -sensitive 1) gene, directly phosphorylates AKT1 through activation by the homologous proteins AtCBL1 and AtCBL9 under low-K + conditions [89,98]. The predicted phosphorylation site of AKT1 is Ser 744 , though this has not been empirically confirmed [25]. Similar regulatory mechanisms exist in rice root tissues; the OsAKT1 channel mediates K + uptake dependent on the OsCBL1-OsCIPK23 complex [108].…”

“…Furthermore, CBLs possess a PFPF motif harboring a conserved serine residue, which is phosphorylated by CIPK at the C-terminus [ 2 , 49 ]. Furthermore, in algal CBLs, some PFPF motifs contain Asp and Glu instead of Ser [ 25 ]. Remarkably, some CBLs harbor the N -myristoylation and palmitoylation sites that usually bind cell membranes [ 39 , 50 ].…”

“…In order to understand CBLs, calcineurin, the Ser/Thr phosphatase that is activated by Ca 2+ and CaM, is important to consider [ 23 ]. In animals and fungi, the regulatory subunit calcineurin B (CnB) and CaM bind with Ca 2+ and interact with the catalytic subunit calcineurin A (CnA) [ 24 , 25 ]. CBLs are similar to CnB but only exist in plants.…”

“…CBLs are similar to CnB but only exist in plants. With a structure similar to that of CnB-CnA, CBLs specifically combine with CBL-interacting protein kinases (CIPKs) to form bimolecular sensor responders involved in Ca 2+ signaling [ 1 , 16 , 25 ]. Notably, the CnB-CnA and CBL–CIPK complexes occur in animals and plants, and understanding their respective functions merits further research.…”