MAPK3 and familial pancreatic carcinoma: In this regard, a negative correlation has been previously found between ERK1/2 activation and the p-Tyr705-STAT3 expression level in pancreatic cancer cells [49]; in addition, ERK or PI3K, the upstream kinase of Akt, can inhibit STAT3 tyrosine phosphorylation in human melanoma cells [50].