Phospho-Stat3 (Ser727) refers to the phosphorylated form of the Stat3 protein at the serine residue 727. This phosphorylation event is significant for the activation of Stat3, a key transcription factor involved in various cellular processes including cell growth, survival, and immune responses. Phosphorylation at Ser727, although often considered a secondary event following Tyr705 phosphorylation, can occur independently and is associated with increased cell survival activity and nuclear translocation of Stat3. It has been shown to play a role in melanocytes and melanoma cells, where Ser727 phosphorylation can precede Tyr705 phosphorylation in the early stages of melanoma progression. Moreover, the constitutive Ser727 phosphorylation in melanoma cells is partially mediated by the B-Raf–MEK–ERK1/2 pathway, indicating its importance in cell survival and nuclear translocation of Stat3 in melanocytic cells. This modification is also implicated in the regulation of gene expression and cellular metabolism, suggesting its role in tumorigenesis and cancer progression.
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