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Molecular and Cellular Biology, May 2001, p. 3387-3397, Vol. 21, No. 10
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.10.3387-3397.2000
Copyright © 2001, American Society for Microbiology. All rights reserved.
JAK2 Activates TFII-I and Regulates Its Interaction
with Extracellular Signal-Regulated Kinase
Dae-Won
Kim and
Brent H.
Cochran*
Department of Cellular and Molecular Physiology, Tufts
University School of Medicine, Boston, Massachusetts 02111
Received 10 January 2001/Accepted 14 February 2001
TFII-I is a transcription factor that shuttles between the
cytoplasm and nucleus and is regulated by serine and tyrosine
phosphorylation. Tyrosine phosphorylation of TFII-I can be regulated in
a signal-dependent manner in various cell types. In B lymphocytes,
Bruton's tyrosine kinase has been identified as a TFII-I tyrosine
kinase. Here we report that JAK2 can phosphorylate and regulate TFII-I
in nonlymphoid cells. The activity of TFII-I on the c-fos
promoter in response to serum can be abolished by dominant negative
JAK2 or the specific JAK2 kinase inhibitor AG490. Consistent with this,
we have also found that JAK2 is activated by serum stimulation of
fibroblasts. Tyrosine 248 of TFII-I is phosphorylated in vivo upon
serum stimulation or JAK2 overexpression, and mutation of tyrosine 248 to phenylalanine inhibits the ability of JAK2 to phosphorylate TFII-I
in vitro. Tyrosine 248 of TFII-I is required for its interaction with
and phosphorylation by ERK and its in vivo activity on the
c-fos promoter. These results indicate that the interaction
between TFII-I and ERK, which is essential for its activity, can be
regulated by JAK2 through phosphorylation of TFII-I at tyrosine 248. Thus, like the STAT factors, TFII-I is a direct substrate of JAK2 and a
signal-dependent transcription factor that integrates signals from both
tyrosine kinase and mitogen-activated protein kinase pathways to
regulate transcription.
*
Corresponding author. Mailing address: Department of
Cellular and Molecular Physiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-0442. Fax: (617)
636-6745. E-mail: cochran{at}opal.tufts.edu.
Molecular and Cellular Biology, May 2001, p. 3387-3397, Vol. 21, No. 10
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.10.3387-3397.2000
Copyright © 2001, American Society for Microbiology. All rights reserved.
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