Published 8 November 2004. doi:10.1083/jcb1673iti1
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 3, 394-394
Escorting STAT5A
Some transcription factors take a chaperone to the nuclear dance. On page 469, Williams et al. show that STAT5A gets this escort from the ERBB4 receptor tyrosine kinase.
ERBB4 becomes an escort upon activation by growth factors such as heregulin (HRG). The activated receptor is known to recruit and phosphorylate STAT5A and get cleaved, thus releasing ERBB4's intracellular domain (4ICD). Williams et al. show that 4ICD remains associated with STAT5A in the cytoplasm. And rather than simply turning on a signal transduction pathway, 4ICD also physically transports STAT5A all the way to the nucleus. Mutation of the 4ICD nuclear localization signal blocked both 4ICD and STAT5A nuclear entry.
In the nucleus, the two remained associated at the promoter of ß-casein, a STAT5A-regulated milk protein gene. ß-Casein transcription was not stimulated unless both 4ICD and STAT5 were nuclear.
Late in pregnancy, ERBB4 replaces the prolactin receptor as the major STAT5A activator. The authors hypothesize that this switch, and STAT5A's resulting interaction with 4ICD, may subtly alter STAT5A-mediated gene expression to bring about terminal differentiation of breast cells. Whether ERBB4 directly transactivates gene expression or can recruit other proteins to the regulated promoters, however, has not been formally tested. 
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone
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J. Cell Biol. 2004 167: 469-478.
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