Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-2-1
pubmed:abstractText
Rapid cell proliferation is a hallmark of transit amplifying cells, but the mechanisms of this localized proliferation are not well understood. The Krüppel-like factor family member Klf5 (IKLF; BTEB2) promotes cell proliferation and is highly expressed in squamous epithelia, in regions of active proliferation. Here, using mouse primary esophageal keratinocytes as a model, we identify a critical role for Klf5 in regulating squamous epithelial proliferation via the epidermal growth factor receptor (EGFR), which, like Klf5, is localized to basal cells in squamous epithelia. We show that Klf5 increases proliferation, transcriptionally up-regulates EGFR, and activates MEK/ERK signaling, as indicated by increased phosphorylation of MEK and ERK. By chromatin immunoprecipitation, we demonstrate that Klf5 binds directly to the 5' regulatory region of EGFR. In addition, we show that regulation of proliferation by Klf5 is dependent on EGFR and MEK/ERK signaling, as the proliferative response to Klf5 is blocked by pharmacologic inhibition of EGFR or MEK. Inhibition of EGFR or MEK also decreases Klf5 expression. Thus, Klf5 regulates MEK/ERK signaling via EGFR and is also downstream of MAPK signaling, providing a novel mechanism for signal amplification or suppression and control of proliferation in basal cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
543-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Krüppel-like factor 5 activates MEK/ERK signaling via EGFR in primary squamous epithelial cells.
pubmed:affiliation
Department of Medicine, Gastroenterology Division, University of Pennsylvania School of Medicine, 415 Curie Blvd., Philadelphia, Pennsylvania 19104-6140, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural