Serine phosphorylation of paxillin by heregulin-β1: Role of p38 mitogen activated protein kinase

Ratna K Vadlamudi, Liana Adam, Amjad Talukder, John Mendelsohn, Rakesh Kumar

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The mechanisms through which heregulin (HRG) regulates the progression of breast cancer cells to a more invasive phenotype are currently unknown. Recently we have shown that HRG treatment of breast cancer cells leads to the formation of lamellipodia/filopodia, and increased cell migration and invasiveness through the phosphatidylinositol 3-kinase (PI-3 kinase). Since the process of cell migration must involve changes in adhesion, we explored the potential HRG regulation of paxillin, a major cytoskeletal phosphoprotein of focal adhesion. We report that HRG stimulation of noninvasive breast cancer cells resulted in stimulation of p38 mitogen-activated protein kinase (p38(MAPK)), extracellular signal-regulated kinases (ERK) and PI-3K, and a concurrent unexpected increase in the level of paxillin phosphorylation on serine residue which was sensitive to protein-phosphatase 2b but not to protein tyrosine phosphatase 1. In addition, HRG triggered a rapid redistribution of paxillin to the perinuclear regions from the tyrosine-phosphorylated focal adhesions. and increased cell scattering. There was no effect of HRG on the state of phosphorylation and localization of focal adhesion kinase. The HRG-induced increase in serine phosphorylation of paxillin and cell scattering were selectively inhibited by a specific inhibitor of p38(MAPK) or a dominant-negative p38(MAPK) mutant, but not by inhibitors of p42/44(MAPK) or PI-3 kinase pathways. For the first time our results have shown that HRG, a potent migratory growth factor stimulates serine phosphorylation of paxillin. These findings suggest a role of p38(MAPK)-dependent signal transduction pathway(s) in serine phosphorylation and disassembly of the paxillin from the focal complexes during HRG-induced cell shape alterations and motility.

Original languageEnglish (US)
Pages (from-to)7253-7264
Number of pages12
JournalOncogene
Volume18
Issue number51
StatePublished - Dec 2 1999
Externally publishedYes

Fingerprint

Neuregulin-1
Paxillin
p38 Mitogen-Activated Protein Kinases
Serine
Phosphorylation
Cell Movement
Pseudopodia
Focal Adhesions
Breast Neoplasms
Phosphatidylinositol 3-Kinase
Protein Phosphatase 1
Focal Adhesion Protein-Tyrosine Kinases
Protein Tyrosine Phosphatases
Cell Shape
Calcineurin
Phosphoproteins
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Phosphatidylinositols
Phosphatidylinositol 3-Kinases

Keywords

  • Heregulin
  • Motility
  • Paxillin
  • Signaling
  • Spreading

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Vadlamudi, R. K., Adam, L., Talukder, A., Mendelsohn, J., & Kumar, R. (1999). Serine phosphorylation of paxillin by heregulin-β1: Role of p38 mitogen activated protein kinase. Oncogene, 18(51), 7253-7264.

Serine phosphorylation of paxillin by heregulin-β1 : Role of p38 mitogen activated protein kinase. / Vadlamudi, Ratna K; Adam, Liana; Talukder, Amjad; Mendelsohn, John; Kumar, Rakesh.

In: Oncogene, Vol. 18, No. 51, 02.12.1999, p. 7253-7264.

Research output: Contribution to journalArticle

Vadlamudi, RK, Adam, L, Talukder, A, Mendelsohn, J & Kumar, R 1999, 'Serine phosphorylation of paxillin by heregulin-β1: Role of p38 mitogen activated protein kinase', Oncogene, vol. 18, no. 51, pp. 7253-7264.
Vadlamudi, Ratna K ; Adam, Liana ; Talukder, Amjad ; Mendelsohn, John ; Kumar, Rakesh. / Serine phosphorylation of paxillin by heregulin-β1 : Role of p38 mitogen activated protein kinase. In: Oncogene. 1999 ; Vol. 18, No. 51. pp. 7253-7264.
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