The functional roles of calcium-dependent protein kinases in plant growth and stress response

Calcium-dependent protein kinases (CPKs/CDPKs) are a multi-gene protein kinase family that play crucial roles in regulating plant growth and stress response. Calcium (Ca2+) is one of the most important secondary messengers, various environmental and developmental cues can stimulate Ca2+ signals, which are displayed in the form of transient changes in calcium ion concentrations. These changes can be recognized and sensed by specific calcium sensors, thereby translating the chemical signals into transcriptional or metabolic processes. In recent years, four classes of calcium sensors have been identified in eukaryotic cells, including calmodulins (CaMs), calmodulin-like proteins (CMLs), calcineurin B-like proteins (CBLs) and CPKs. Among these calcium sensors, CaMs are highly conserved in all eukaryotic cells, whereas the others are only identified in plants and some protists. Particularly, CPKs are commonly expressed in plants, but not in animal cells. These calcium sensors, together with other key components in Ca2+ signaling pathways, can recognize specific calcium signatures and trigger downstream signaling events, such as reprogramming of transcriptional processes, activation of receptor like kinase cascades, and accumulation of ROS. In addition, these calcium sensors display distinct protein structures and activation mechanisms. CaMs, CMLs and CBLs solely have a Ca2+ binding domain and function as sensors by directly binding to Ca2+ ions. While CPKs have four characterized domains, including a variable N-terminal domain, a Ser/Thr kinase catalytic domain, an autoregulatory/autoinhibitory domain and a calmodulin-like domain. Further, CPKs are the only calcium sensors that have a protein kinase activating domain. The cytosolic Ca2+ signals can be sensed by CPKs and followed by calcium-dependent conformation changes. In this regard, CPKs function as direct "sensor decoders" for translating Ca2+ signals. In plants, CPKs convey calcium signals into cellular responses by phosphorylating various substrates, including membrane transporters, kinases, transcription factors, metabolic enzymes, etc. Interestingly, recent studies revealed that CPKs can autophosphorylate on Ser and Thr amino acids both in vivo and in vitro, whereas very few CPKs autophosphorylate on Tyr residues. This huge diversity of phosphorylation targets confers key functions of CPKs in cell division, pollen tube growth, stomatal development, phytohormone signaling, transcriptional regulation, stress defense, etc. Importantly, specificities in CPK signaling are determined by differential expression patterns, calcium binding selectivity, subcellular localizations and substrates. In the past years, various CPK families have been discovered in model plant systems and crops. For instance, the Arabidopsis (Arabidopsis thaliana) genome encodes 34 CPKs that are characterized by their isoform specificities and calcium-dependent kinase activities. Despite extensive studies have been performed to elucidate CPKs' functions and Ca2+-CPKs signaling networks, the molecular mechanisms of most CPK genes remain poorly understood. In this review, we will describe the structures, subcellular localizations and molecular characteristics of CPKs, we focus on the functional roles of CPKs in regulating plant growth, phytohormone signaling and stress tolerance. Finally, we will discuss future directions in the studies of how CPKs determine crop quality and agronomic traits.