MITF is phosphorylated on several serine and tyrosine residues. Serine phosphorylation is regulated by several signaling pathways including MAPK/BRAF/ERK, receptor tyrosine kinase KIT, GSK-3 and mTOR. In addition, several kinases including PI3K, AKT, SRC and P38 are also critical activators of MITF phosphorylation. In contrast, tyrosine phosphorylation is induced by the presence of the KIT oncogenic mutation D816V. This KIT pathway is dependent on SRC protein family activation signaling. The induction of serine phosphorylation by the frequently altered MAPK/BRAF pathway and the GSK-3 pathway in melanoma regulates MITF nuclear export and thereby decreasing MITF activity in the nucleus. Similarly, tyrosine phosphorylation mediated by the presence of the KIT oncogenic mutation D816V also increases the presence of MITF in the cytoplasm.