A transformation-associated complex involving tyrosine kinase signal adapter proteins and caldesmon links v-ErbB signaling to actin stress fiber disassembly

Michael J. Mcmanus, Wilma L. Lingle, Jeffrey L. Salisbury, Nita Jane Maihle

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The avian erythroblastosis viral oncogene (v-erbB) encodes a receptor tyrosine kinase that possesses sarcomagenic and leukemogenic potential. We have expressed transforming and nontransforming mutants of v-erbB in fibroblasts to detect transformation-associated signal transduction events. Coimmunoprecipitation and affinity chromatography have been used to identify a transformation-associated, tyrosine phosphorylated, multiprotein complex. This complex consists of Src homologous collagen protein (Shc), growth factor receptor binding protein 2 (Grb2), son of sevenless (Sos), and a novel tyrosine phosphorylated form of the cytoskeletal regulatory protein caldesmon. Immunofluorescence localization studies further reveal that, in contrast to the distribution of caldesmon along actin stress fibers in normal fibroblasts, caldesmon colocalizes with Shc in plasma membrane blebs in transformed fibroblasts. This colocalization of caldesmon and Shc correlates with actin stress fiber disassembly and v-erbB-mediated transformation. The tyrosine phosphorylation of caldesmon, and its association with the Shc- Grb2-Sos signaling complex directly links tyrosine kinase oncogenic signaling events with cytoskeletal regulatory processes, and may define one mechanism regulating actin stress fiber disassembly in transformed cells.

Original languageEnglish (US)
Pages (from-to)11351-11356
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number21
DOIs
StatePublished - Oct 14 1997

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Calmodulin-Binding Proteins
Stress Fibers
Protein-Tyrosine Kinases
Actins
Collagen
Tyrosine
Growth Factor Receptors
Fibroblasts
Carrier Proteins
Proteins
erbB-1 Genes
Multiprotein Complexes
Cytoskeletal Proteins
Receptor Protein-Tyrosine Kinases
Blister
Affinity Chromatography
Fluorescent Antibody Technique
Signal Transduction
Phosphorylation
Cell Membrane

ASJC Scopus subject areas

  • General

Cite this

A transformation-associated complex involving tyrosine kinase signal adapter proteins and caldesmon links v-ErbB signaling to actin stress fiber disassembly. / Mcmanus, Michael J.; Lingle, Wilma L.; Salisbury, Jeffrey L.; Maihle, Nita Jane.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 21, 14.10.1997, p. 11351-11356.

Research output: Contribution to journalArticle

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