Faculty Collaboration Database

Activation of the Jak2-Stat5 signaling pathway in Nb2 lymphoma cells by an anti-apoptotic agent, aurintricarboxylic acid. J Biol Chem 1998 Jan 02;273(1):28-32

Date

02/07/1998

Pubmed ID

9417042

DOI

10.1074/jbc.273.1.28

Scopus ID

2-s2.0-0031982630 (requires institutional sign-in at Scopus site)   61 Citations

Abstract

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.

Author List

Rui H, Xu J, Mehta S, Fang H, Williams J, Dong F, Grimley PM

MESH terms used to index this publication - Major topics in bold

Apoptosis
Aurintricarboxylic Acid
Calcium-Calmodulin-Dependent Protein Kinases
DNA
DNA-Binding Proteins
Enzyme Activation
Gene Expression Regulation
Janus Kinase 2
Lymphocytes
Lymphoma
Milk Proteins
Phosphorylation
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-pim-1
Receptors, Prolactin
STAT5 Transcription Factor
Signal Transduction
Trans-Activators
Tumor Cells, Cultured
Tyrosine