Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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 factor and c-Kit, is essential for melanocyte development. This cascade results in increased Mi-dependent transcriptional reporter 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 transcriptional 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.

Type

Journal article

Publication Date

1998

Volume

273

Pages

17983 - 17986

Keywords

Animal Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism Dimerization DNA-Binding Proteins/genetics/*physiology Enzyme Activation Hamsters Human Melanocytes/*physiology Mice Nuclear Proteins/*physiology Phosphorylation Protein Binding Proto-Oncogene Proteins c-kit/physiology Rabbits *Signal Transduction Stem Cell Factor/physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activation (Genetics) Trans-Activators/*physiology Transcription Factors/*physiology Tumor Cells, Cultured