An oncogenic epidermal growth factor receptor signals via a p21-activated kinase-caldesmon-myosin phosphotyrosine complex

Michael J. McManus, Julie L. Boerner, Andrew J. Danielsen, Ze Wang, Fumio Matsumura, Nita J. Maihle

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Many ligand-independent receptor tyrosine kinases are tumorigenic. The biochemical signals that mediate ligand-independent transformation of cells by these transmembrane receptors are poorly defined. In this report, we demonstrate that a constitutively activated mutant epidermal growth factor receptor (v-ErbB) induces the formation of a transformation-specific signaling module that complexes with myosin II. The components of this signaling complex include the signal adapter proteins Shc, Grb2, and Nck, and tyrosine-phosphorylated forms of p21-activated kinase (Pak), caldesmon, and myosin light chain kinase. Transformation-specific, tyrosine phosphorylation of Pak enhances the catalytic activity of this serine/threonine kinase. Furthermore, the tyrosine phosphorylation of Pak is Rho-, but not Ras-, Rac-, or Cdc42-dependent. These results demonstrate that a ligand-independent epidermal growth factor receptor mutant can transduce oncogenic signals that are distinct from ligand-dependent, mitogenic signals. In addition, these data provide evidence for the coupling of oncogenic receptor tyrosine kinases with the actomyosin molecular motor. This myosin-associated signaling module may mediate some of the biochemical changes of myosin found in v-ErbB-transformed fibroblasts, thereby contributing to the regulation of the mechanical forces governing cellular adhesion, cytoskeletal tension, and, hence, anchorage-independent cell growth.

Original languageEnglish (US)
Pages (from-to)35328-35334
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number45
DOIs
StatePublished - Nov 10 2000
Externally publishedYes

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p21-Activated Kinases
Calmodulin-Binding Proteins
Phosphotyrosine
Myosins
Epidermal Growth Factor Receptor
Ligands
Tyrosine
Phosphorylation
Receptor Protein-Tyrosine Kinases
Myosin Type II
Myosin-Light-Chain Kinase
Actomyosin
Protein-Serine-Threonine Kinases
Cell growth
Fibroblasts
Catalyst activity
Adhesion
Cells
Growth
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

An oncogenic epidermal growth factor receptor signals via a p21-activated kinase-caldesmon-myosin phosphotyrosine complex. / McManus, Michael J.; Boerner, Julie L.; Danielsen, Andrew J.; Wang, Ze; Matsumura, Fumio; Maihle, Nita J.

In: Journal of Biological Chemistry, Vol. 275, No. 45, 10.11.2000, p. 35328-35334.

Research output: Contribution to journalArticle

McManus, Michael J. ; Boerner, Julie L. ; Danielsen, Andrew J. ; Wang, Ze ; Matsumura, Fumio ; Maihle, Nita J. / An oncogenic epidermal growth factor receptor signals via a p21-activated kinase-caldesmon-myosin phosphotyrosine complex. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 45. pp. 35328-35334.
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