TY - JOUR
T1 - Lineage-specific signaling in melanocytes. c-Kit stimulation recruits p300/CBP to microphthalmia
AU - Price, E. Roydon
AU - Ding, Han Fei
AU - Badalian, Tina
AU - Bhattacharya, Shoumo
AU - Takemoto, Clifford M
AU - Yao, Tso Pang
AU - Hemesath, Timothy J.
AU - Fisher, David E.
PY - 1998/7/17
Y1 - 1998/7/17
N2 - During melanocyte development, the cytokine Steel factor activates its receptor c-Kit, initiating a signal transduction cascade, which is vital for lineage determination via unknown downstream nuclear targets. c-Kit has recently been found to trigger mitogen-activated protein kinase-mediated phosphorylation of Microphthalmia (Mi), a lineage-restricted transcription factor, which, like steel facto and c-Kit, is essential for melanocyte development. This cascade results in increased Mi-dependent tanscriptional reported activity. Here we examine the mechanism by which Mi is activated by this pathway. Phosphorylation does not significantly alter Mi's nuclear localization, DNa binding, or dimerization. However, the tanscriptional coactivator p300/CBP selectively associates with mitogen-activated protein kinase-phosphorylated Mi, even under conditions in which non-MAPK phospho-Mi is more abundant. Moreover, p300/CBP coactivates Mi transcriptional activity in a manner dependent upon this phosphorylation. Mi thus joins CREB as a transcription factor whose signal-responsive phosphorylation regulates coactivator recruitment, in this case modulating lineage development in melanocytes.
AB - During melanocyte development, the cytokine Steel factor activates its receptor c-Kit, initiating a signal transduction cascade, which is vital for lineage determination via unknown downstream nuclear targets. c-Kit has recently been found to trigger mitogen-activated protein kinase-mediated phosphorylation of Microphthalmia (Mi), a lineage-restricted transcription factor, which, like steel facto and c-Kit, is essential for melanocyte development. This cascade results in increased Mi-dependent tanscriptional reported activity. Here we examine the mechanism by which Mi is activated by this pathway. Phosphorylation does not significantly alter Mi's nuclear localization, DNa binding, or dimerization. However, the tanscriptional coactivator p300/CBP selectively associates with mitogen-activated protein kinase-phosphorylated Mi, even under conditions in which non-MAPK phospho-Mi is more abundant. Moreover, p300/CBP coactivates Mi transcriptional activity in a manner dependent upon this phosphorylation. Mi thus joins CREB as a transcription factor whose signal-responsive phosphorylation regulates coactivator recruitment, in this case modulating lineage development in melanocytes.
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U2 - 10.1074/jbc.273.29.17983
DO - 10.1074/jbc.273.29.17983
M3 - Article
C2 - 9660747
AN - SCOPUS:0032541068
SN - 0021-9258
VL - 273
SP - 17983
EP - 17986
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 29
ER -