Identifier: R-HSA-9824994
MITF-M is phosphorylated by RPS6KA1 (also known as RSK1) at serine S409 downstream of activated SCF-KIT signaling during development (Wu et al, 2000). S409 phosphorylation primes MITF-M for subsequent phosphorylation by GSK3B at serine residues S397, S401 and S405 in the C-terminus, modifications that are associated with degradation of the protein (Ploper et al, 2015, reviewed in Goding and Arnheiter, 2019).
The relationship between MITF and KITLG-KIT during melanocyte differentiation is not totally clear. Mutations of KIT or its ligand are associated with pigmentation defects and depleted levels of mature melanocytes. KIT signaling appears to contribute to the migration and survival of melanoblasts during development (Wehrle-Haller and Weston, 1995; Wehrle-Haller et al, 2001; Tabone-Eglinger et al, 2012; Kunisada et al, 1998; reviewed in White and Zon, 2008). MITF-M and KIT also appear to reciprocally affect each other's expression: although KIT does not appear to be required for the initial expression of MITF during development, activated KIT signaling increases the transcription factor activity of MITF to a variable extent at different MITF-M target genes (Hou et al, 2000; Price et al, 1998, Wu et al, 2000, Hemesath et al, 1998). Similarly, expression of MITF-M has been shown to increase expression of KIT in some systems (Tsujimura et al, 1996; Opdecamp et al, 1997; reviewed in Hou and Pavan, 2008)