## 2 Results
### Eukaryotic-Like Serine or Threonine Protein Kinases  
The genome of _S. coelicolor_ and _S. lividans_ contain numerous genes encoding eukaryotic-like serine or threonine protein kinases (ESTPK) [188; 189]. In this study, 23 ESTPK were detected and can be classified into three main clusters (a, b, c, Figure 10).  
The 5 proteins of cluster a were more abundant in _SL_ than in _SC_ in Pi proficiency or limitation. Two proteins were rather more abundant in Pi proficiency than in Pi limitation, whereas it was the opposite for 3 others, including the putative membrane-associated sensory kinase RamC/SCO6681 [190]. RamC is encoded by the first gene of the _ramCSAB_ operon that includes _ramS/supB_ encoding the morphogenetic peptide RamS and components of an ABC transporter (RamAB). These proteins are necessary for morphological  
Figure 9: Cluster H, heatmap representation of transcriptional regulators and sensory histidine kinases more abundant in Pi limitation than in Pi proficiency in _SL_ but not in _SC_.  
differentiation but not for vegetative growth nor antibiotic biosynthesis and their expression is under the positive control of the response regulator RamR [162; 191].  
The 11 proteins of cluster b were more abundant in _SC_ than in _SL_ in both Pi conditions. This cluster includes four of the five kinases belonging to the sco4775-sco4779 cluster encoding PkaH/SCO4775, SCO4776, PkaD/SCO4777, PkaI/SCO4778 (not detected), and Pkaj/SCO4779. Two of these EPK (PkaH and Pkal) were shown to be part of the spore wall synthesizing multi-protein complex SSSC which includes proteins directing peptidoglycan (MreBCD, PBP2, Sfr, RodZ) and cell wall glycopolymer synthesis (PdtA) [192]. Pkal and PkaH/SCO4775 were shown to phosphorylate MreC [193]. The high abundance of these proteins in _SC_ might be related to the cell wall stress occurring in these bacteria. This cluster also includes PglW/SCO6626, which, together with PgIY (ATPase), PgIX (DNA methylase), and PgIZ (inhibitor of PgIX activity), is part of a phage growth limitation (Pgl) system that confers protection against the temperate bacteriophage phiC31 and its relatives [194]. PgIW was proposed to transduce a signal, probably via phosphorylation, to other PgI proteins resulting in the activation of the DNA methyltransferase PglX leading to phage restriction [195].  
The 7 proteins of cluster c were more abundant in _SC_ than in _SL_ but mainly in Pi limitation at both time points. However, 4 of these proteins were also abundant in Pi limitation, in _SL_ at 48 h. This cluster includes:  
* AfsK/SCO4423 which phosphorylates, together with other ESTPK [196], AfsR/SCO4426, a global regulator, that has a positive impact on antibiotic biosynthesis [153] and morphological differentiation [154; 155]. AfsK was also shown to phosphorylate the DnaA initiator protein impairing its interaction with the replication origin and thus inhibiting replication [197].  
Figure 10: Heatmap representation of the abundance of eukaryotic-like serine or threonine protein kinases in _SL_ and _SC_ that can be divided in 3 sub-clusters, a, b and c. The 5 proteins of cluster a were more abundant in _SL_ than in _SC_ in Pi proficiency or limitation. The 11 proteins of cluster b were more abundant in _SC_ than in _SL_ in both Pi conditions. The 7 proteins of cluster c were more abundant in _SC_ than in _SL_ in Pi limitation at both time points but 4 of these proteins were also abundant in Pi limitation, in _SL_ at 48 h.  
PkaF/SCO2110, whose over-expression was shown to be correlated with a strong reduction of ACT (but not of RED) biosynthesis and an inhibition of morphological differentiation, suggesting that it plays a negative role in the regulation of these processes [198].