Figure 6. Model of STATc activation in response to hyperosmotic conditions.

The model is based on results from previously published studies (green) and from results (blue) and educated assumptions (red) of the present work. In response to hyperosmolarity intracellular cGMP and Ca²⁺ act in parallel as second messengers in order to activate STATc. GbpC is downstream of cGMP and we postulate that it acts upstream of Pyk3 and an as yet unidentified STATc protein kinase (SPK). Phg2 inhibits PTP3 either directly or indirectly by phosphorylation of S747 and an unknown additional PTP3 serine/threonine protein kinase (PPK) must be responsible for phosphorylation of PTP3 at S448. These protein kinases are under control of the Ca²⁺ branch of the STATc signaling cascade [7]. The model does not satisfactorily explain all experimental results and we additionally propose a crosstalk between the two signaling branches (not shown). See the Discussion section for further details of this model.