Peptide hormones play pivotal roles in many physiological processes through coordinating developmental and environmental cues among different cells. Peptide hormones are recognized by their receptors that convey signals to downstream targets and interact with multiple pathways to fine-tune plant growth. Extensive research has illustrated the mechanisms of peptides in shoots but functional studies of peptides in roots are scarce. Reactive oxygen species (ROS) are known to be involved in stress-related events. However, recent studies have shown that they are also associated with many processes that regulate plant development. Here, we focus on recent advances in understanding the relationships between peptide hormones and their receptors during root growth including outlines of how ROS are integrated with these networks.

Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non‐small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of EGFR TKIs. In this study, our data showed that chronic exposure to cigarette smoke extract (CSE) or tobacco smoke‐derived carcinogen benzo[α]pyrene, B[α]P, but not nicotine‐derived nitrosamine ketone (NNK), reduced the sensitivity of wild‐type EGFR‐expressing NSCLC cells to EGFR TKIs. Treatment with TKIs almost abolished EGFR tyrosine kinase activity but did not show an inhibitory effect on downstream Akt and ERK pathways in B[α]P‐treated NSCLC cells. CSE and B[α]P transcriptionally upregulate c‐MET and activate its downstream Akt pathway, which is not inhibited by EGFR TKIs. Silencing of c‐MET reduces B[α]P‐induced Akt activation. The CSE‐treated NSCLC cells are sensitive to the c‐MET inhibitor crizotinib. These findings suggest that cigarette smoke augments oncogene addiction to c‐MET in NSCLC cells and that MET inhibitors may show clinical benefits for lung cancer patients with a smoking history.

The Root meristem growth factor 1 (RGF1) peptide extends the PLETHORA2 (PLT2) protein gradient by altering the distinct localization of superoxide (O2−) and hydrogen peroxide (H2O2) among the root developmental zones. However, the underlying mechanism through which reactive oxygen species (ROS) regulate PLT2 stability is unclear. Here, we demonstrate that the 212th cysteine of PLT2 is pivotal in modulating PLT2 stability through ROS. The PLT2 protein concentration gradient rapidly decreases in the elongation zone, where H2O2 accumulation initiates. However, substituting the 212th cysteine of PLT2 with serine (PLT2C212S) results in PLT2 being more stable in the elongation zone, more broadly localized by RGF1, and showing robust resistance to H2O2. The sulfenylation of PLT2 was detected following treatment with H2O2 at high concentrations, suggesting that S-sulfenylation of the 212th cysteine controls PLT2 protein stability through local ROS distributions. These findings show that the formation of the PLT2 concentration gradient through ROS depends on a PLT2 sulfenylation mechanism that involves the 212th cysteine.

The protein concentration gradients of the master regulators of the root meristem, named the PLETHORA proteins, modulate the root meristem size. Root meristem growth factor 1 (RGF1) peptide extends the PLETHORA2 (PLT2) protein gradients by altering reactive oxygen species (ROS) distributions. However, the underlying mechanism through which the ROS alterations regulate PLT2 remains unknown. Here, we demonstrate that the 212 ^th cysteine of the PLT2 protein plays a pivotal role in modulating PLT2 stability through the ROS altered by RGF1. The substitution of the 212 ^th cysteine of PLT2 with serine (PLT2 ^C212S ) enhanced the PLT2 protein stability upon RGF1 and resulted in robust resistance to ROS relative to the native PLT2. Accordingly, PLT2 ^C212S modulated expressions of certain specific root development-related genes to a greater extent than native PLT2. In summary, these findings show that the PLT2 concentration gradient formation through ROS, modulated by RGF1, is dependent on a mechanism involving the 212 ^th cysteine of PLT2.