Src tyrosyl phosphorylates cortactin in response to prolactin.

Abstract

The hormone/cytokine prolactin (PRL) is implicated in breast cancer cell invasion and metastasis. PRL-induced pathways are mediated by two non-receptor tyrosine kinases, JAK2 and Src. We previously demonstrated that prolactin stimulates invasion of breast cancer cells TMX2-28 through JAK2 and its target serine/threonine kinase PAK1. We hypothesize herein that the actin-binding protein cortactin, a protein involved in invadopodia formation and cell invasion, is activated by PRL. We demonstrate that TMX2-28 cells are more invasive than T47D breast cancer cells in response to PRL. We determine that cortactin is tyrosyl phosphorylated in response to PRL in a time and dose-dependent manner in TMX2-28 cells, but not in T47D cells. Furthermore, we show that PRL mediates cortactin tyrosyl phosphorylation via Src, but not JAK2. Finally, we demonstrate that maximal PRL-mediated TMX2-28 cell invasion requires both Src and JAK2 kinase activity, while T47D cell invasion is JAK2- but not Src-dependent. Thus PRL may induce cell invasion via two pathways: through a JAK2/PAK1 mediated pathway that we have previously demonstrated, and Src-dependent activation and tyrosyl phosphorylation of cortactin.

• Authors: Alan Hammer, Sneha Laghate, Maria Diakonova
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 463 Issue 4 Pg. 644-9 (Aug 07 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26043691 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Cortactin
• Tyrosine
• Prolactin
• src-Family Kinases

Topics

• Cortactin (metabolism)
• Humans
• MCF-7 Cells
• Phosphorylation
• Prolactin (physiology)
• Tyrosine (metabolism)
• src-Family Kinases (metabolism)