In the renal collecting duct, binding of arginine vasopressin (AVP) to the V2 receptor triggers signaling changes that regulate osmotic water transport. Short-term regulation of water transport is dependent on vasopressin-induced phosphorylation of aquaporin-2 (AQP2) at Ser256. The protein kinase that phosphorylates this site is not known. Here we use Bayes' theorem to rank all 521 rat protein kinases with regard to the likelihood of a role in Ser256 phosphorylation based on prior data and new experimental data. First, prior probabilities were estimated from previous transcriptomic and proteomic profiling data, kinase substrate specificity data, and evidence for kinase regulation by vasopressin. This ranking was updated using new experimental data describing the effects of several small-molecule kinase inhibitors with known inhibitory spectra (H89, KN62, KN93, and GSK-650394) on Ser256-AQP2 phosphorylation in inner medullary collecting duct suspensions. The top-ranked kinase was calcium/calmodulin-dependent protein kinase II (CAMK2) followed by protein kinase A (PKA) and protein kinase B (AKT). LC-MS/MS-based in vitro phosphorylation studies compared the ability of three highly ranked kinases to phosphorylate AQP2 and other IMCD proteins, viz. PKA, CAMK2 and serum/glucocorticoid-regulated kinase (SGK). All three proved capable of phosphorylating Ser256, although both CAMK2 and PKA were more potent than SGK. The in vitro phosphorylation experiments also identified candidate protein kinases for several additional phosphoproteins with likely roles in collecting duct regulation including Nedd 4-2, Map4k4 and 3-phosphoinositide-dependent protein kinase 1. We conclude that the use of Bayes' theorem is an effective means of integrating data from multiple data sets in physiology.