PMID- 10353695 OWN - NLM STAT- MEDLINE DCOM- 19990803 LR - 20190921 IS - 0898-6568 (Print) IS - 0898-6568 (Linking) VI - 11 IP - 3 DP - 1999 Mar TI - Prolactin-independent modulation of the beta-casein response element by Erk2 MAP kinase. PG - 205-10 AB - The MAP kinases have been suggested to play a role in intracellular signalling by PRL. A reporter gene construct, PRE3-CAT, which manifests PRL responsiveness through a Stat5-binding site (PRE), was induced by PRL in CHO cells expressing the PRL-R. A fusion protein (Gal4-Stat5(695)), containing the C-terminal domain of Stat5a (amino acids 695-794) linked to the DNA-binding domain of Gal4 (Gal4 DBD), strongly activated transcription of a luciferase reporter gene. Therefore, the Stat5 C-terminus, which contains a potential MAP kinase phosphorylation site, exhibits a modular transactivating function. A kinase-defective mutant of Erk2 (iMAPK) caused a dose-dependent suppression of PRL-stimulated PRE3-CAT, and also inhibited the induction of PRE3-CAT by Jak2 over-expression. Correspondingly, over-expression of the MAP kinase activator v-Src increased the PRL-stimulated level of PRE3-CAT. Gal4-Stat5(695) activity was not modulated by PRL or Jak2, consistent with the absence of the relevant tyrosine phosphorylation site at residue 694. Gal4-Stat5(695) was not inhibited by iMAPK, indicating that the C-terminal transactivation region of Stat5a is not sensitive to direct modulation of a MAP kinase pathway. These results suggest that alteration of Erk2 activity by growth factors may modulate PRL-induced gene expression by a mechanism upstream of Stat5. FAU - Gao, J AU - Gao J AD - Department of Molecular and Cellular Physiology, University of Cincinnati, OH 45267-0576, USA. FAU - Horseman, N D AU - Horseman ND LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Caseins) RN - 0 (DNA-Binding Proteins) RN - 0 (Milk Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (STAT5 Transcription Factor) RN - 0 (Trans-Activators) RN - 9002-62-4 (Prolactin) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Janus Kinase 2) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) SB - IM MH - Animals MH - CHO Cells MH - Calcium-Calmodulin-Dependent Protein Kinases/*physiology MH - Caseins/*metabolism MH - Cricetinae MH - DNA-Binding Proteins/metabolism MH - Janus Kinase 2 MH - *Milk Proteins MH - Mitogen-Activated Protein Kinase 1 MH - Models, Biological MH - Prolactin/*physiology MH - Protein-Tyrosine Kinases/metabolism MH - *Proto-Oncogene Proteins MH - STAT5 Transcription Factor MH - Signal Transduction MH - Trans-Activators/metabolism MH - Transfection EDAT- 1999/06/03 00:00 MHDA- 1999/06/03 00:01 CRDT- 1999/06/03 00:00 PHST- 1999/06/03 00:00 [pubmed] PHST- 1999/06/03 00:01 [medline] PHST- 1999/06/03 00:00 [entrez] AID - S0898-6568(98)00067-9 [pii] AID - 10.1016/s0898-6568(98)00067-9 [doi] PST - ppublish SO - Cell Signal. 1999 Mar;11(3):205-10. doi: 10.1016/s0898-6568(98)00067-9.