Streptococcus pneumoniae is an opportunistic human pathogen which encodes a single eukaryotic-type Ser/Thr protein kinase StkP and its functional counterpart protein phosphatase PhpP. These signalling enzymes play a crucial role in the coordination of cell division and growth in pneumococcus. In this study, we determined the proteomic and phosphoproteomic profiles of relevant mutants. A comparison with the wild type provided a representative data set of new phosphoacceptor sites and StkP-dependent substrates. StkP phosphorylates key proteins involved in cell division and cell wall biosynthesis in unencapsulated laboratory Rx1 strain as well as encapsulated virulent strain D39. Moreover, we show that StkP plays important role in eliciting an adaptive response induced by cell wall directed antibiotic. Phosphorylation of WalK sensor kinase and decline of the abundance of WalK and proteins of core WalR/K regulon implies cross-talk between StkP and WalR/K two-component system. Inspection of proteome profiles revealed gene clusters regulated by catabolite control mechanism suggesting a tight coupling of carbon flow and cell wall homeostasis. The disbalance of steady-state protein phosphorylation in the mutants as well as after antibiotic treatment is accompanied by accumulation of global Spx regulator indicating Spx-mediated envelope stress response. In summary, StkP translates the sensed signal about the cell-wall status to key cell division and regulatory proteins and in this way controls cell cycle and cell wall homeostasis.