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Vol. 273, Issue 1, 28-32, January 2, 1998
From the Department of Pathology, Uniformed Services University of
the Health Sciences, Bethesda, Maryland 20814
Biological effects of many hormones and cytokines
are mediated through receptor-associated Jak tyrosine kinases and
cytoplasmic Stat transcription factors, including critical
physiological processes such as immunity, reproduction, and cell growth
and differentiation. Pharmaceuticals that control Jak-Stat pathways are
therefore of considerable interest. Here we demonstrate that a single
Jak-Stat pathway can be activated by aurintricarboxylic acid (ATA), a
negatively charged triphenylmethane derivative (475 Da) with
anti-apoptotic properties. In prolactin (PRL)-dependent Nb2
lymphocytes, ATA sustained cell growth in the absence of hormone and
mimicked rapid PRL-induced tyrosine phosphorylation of Jak2 and
activation of Stat5a and Stat5b with tyrosine phosphorylation,
heterodimerization, DNA binding, and induction of the Stat5-regulated
pim-1 protooncogene. ATA also mimicked PRL activation of
serine kinases ERK1 and ERK2. However, unlike PRL, ATA did not regulate
Stat1 or Stat3. ATA also did not affect Jak3, which is activated in
these cells by interleukin-2 family cytokines. Although the mechanism
and specificity by which ATA activates Jak2, Stat5, and ERKs in Nb2
cells are still unclear, the present study demonstrates that certain
hormone or cytokine effects on Jak-Stat pathways can be discretely
imitated by a low molecular weight, non-peptide pharmaceutical. The
results are also consistent with Stat5 involvement in lymphocyte growth and survival.
This article has been cited by other articles:
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R. Beery, M. Haimsohn, N. Wertheim, R. Hemi, U. Nir, A. Karasik, H. Kanety, and A. Geier Activation of the Insulin-Like Growth Factor 1 Signaling Pathway by the Antiapoptotic Agents Aurintricarboxylic Acid and Evans Blue Endocrinology, July 1, 2001; 142(7): 3098 - 3107. [Abstract] [Full Text] [PDF]
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 I. C. CHIKANZA Prolactin and Neuroimmunomodulation: In Vitro and in Vivo Observations Ann. N.Y. Acad. Sci., June 22, 1999; 876(1): 119 - 130. [Abstract] [Full Text] [PDF]
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H. Yamashita, J. Xu, R. A. Erwin, A. C. Larner, and H. Rui A Lymphoma Growth Inhibitor Blocks Some but Not All Prolactin-stimulated Signaling Pathways J. Biol. Chem., May 21, 1999; 274(21): 14699 - 14705. [Abstract] [Full Text] [PDF]
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H. Yamashita, J. Xu, R. A. Erwin, W. L. Farrar, R. A. Kirken, and H. Rui Differential Control of the Phosphorylation State of Proline-juxtaposed Serine Residues Ser725 of Stat5a and Ser730 of Stat5b in Prolactin-sensitive Cells J. Biol. Chem., November 13, 1998; 273(46): 30218 - 30224. [Abstract] [Full Text] [PDF]
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