Can the two carboxypeptidase inhibitors of tomato act as signalling peptides during fruit development?

The tomato TCMP-1 and TCMP-2 genes code for metallocarboxypeptidase inhibitors, a subclass of the cystine-knot peptides family. The two transcripts display a sequential expression during flower/fruit development, with TCMP-1 highly expressed in flower buds before anthesis and TCMP-2 in ripe fruits. The alteration of their endogenous levels by expressing the TCMP-1 coding sequence under the control of the TCMP-2 promoter revealed that their relative levels are crucial for the fruit set timing (Molesini et al., 2018). The two mature TCMPs are 32% identical and highly similar in structure to the potato carboxypeptidase inhibitor (PCI). Both TCMPs and PCI share structural homology with some mammalian growth factors such as the epidermal growth factor (EGF) and vascular epidermal growth factor (VEGF), and are bioactive in mammalian cells. PCI competes with EGF for the binding to EGF receptor, inhibiting its activation (Blanco-Aparicio et al., 1998); TCMPs inhibit angiogenesis both in vitro in human umbilical vascular cells and in vivo in zebrafish by affecting the VEGF receptor activation (Cavallini et al., 2011; Treggiari et al., 2015). Thus, TCMPs can interfere with growth factor signalling pathways in animal cells. We can speculate that TCMPs could exert a similar activity also in plant cells. By sequence comparison we searched for plant receptors containing extracellular EGF-like domains that could represent good candidates for TCMPs recognition. EGF repeats in plants are found in receptor-like kinases of the wall-associated kinases-type (WAKs-type) and S-locus receptor kinases-type (SRKs-type). WAK and SRK members are shown to be involved in stress responses but also in growth and development.