Phosphotyrosyl proteins in childhood rhabdomyosarcomas: Phosphorylation of catenins and components of the insulin-like growth factor type I receptor signaling cascade

Michael J. McManus, P. Jesse Hutt, Nita Jane Maihle

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: Rhabdomyosarcomas (RMS) are heterogeneous in their clinical presentation, histology, and cytogenetics. The growth of some RMS cells has been found to be regulated by the tyrosine kinase insulin-like growth factor (IGF) type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of tyrosine kinases and IGF receptors. Collectively, these heterogeneous features suggest that differences exist in the growth regulatory pathways of RMS. The objective of this study is to identify active tyrosine kinase signal transduction pathways in embryonal and alveolar RMS cells. Methods: RMS tumor samples and cell lines representing both embryonal and alveolar histologic subtypes have been analyzed by immunoprecipitation and immunoblotting techniques to characterize phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins. Results: RMS cells can be characterized based on the patterns of phosphotyrosyl proteins, including the phosphorylation status of the catenin-like protein Cas 1 and the signal adapter protein SHC, and the activation of IGF type I receptor signaling cascades including the formation of SHC-GRB2 signal protein complexes and MAP kinase activation. Conclusions: Rhabdomyosarcomas, especially the embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase signal transduction. It will be important to characterize the growth regulatory pathways active in individual RMS tumors before targeting molecular therapies to this malignancy.

Original languageEnglish (US)
Pages (from-to)319-326
Number of pages8
JournalAmerican Journal of Pediatric Hematology/Oncology
Volume19
Issue number4
DOIs
StatePublished - Jan 1 1997

Fingerprint

Catenins
IGF Type 1 Receptor
Rhabdomyosarcoma
Phosphorylation
Protein-Tyrosine Kinases
Embryonal Rhabdomyosarcoma
Proteins
Signal Transduction
Growth
Alveolar Rhabdomyosarcoma
Somatomedin Receptors
Alveolar Epithelial Cells
Tumor Cell Line
Immunoprecipitation
Immunoblotting
Cytogenetics
Tyrosine
Neoplasms
Histology
Phosphotransferases

Keywords

  • Cas 1
  • Insulin-like growth factor type I receptor
  • Phosphotyrosyl proteins
  • Rhabdomyosarcoma
  • SHC
  • Signal transduction pathways
  • Tyrosine kinases

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Phosphotyrosyl proteins in childhood rhabdomyosarcomas : Phosphorylation of catenins and components of the insulin-like growth factor type I receptor signaling cascade. / McManus, Michael J.; Hutt, P. Jesse; Maihle, Nita Jane.

In: American Journal of Pediatric Hematology/Oncology, Vol. 19, No. 4, 01.01.1997, p. 319-326.

Research output: Contribution to journalArticle

@article{4ac19dee5cff468db7a464330c7cbebe,
title = "Phosphotyrosyl proteins in childhood rhabdomyosarcomas: Phosphorylation of catenins and components of the insulin-like growth factor type I receptor signaling cascade",
abstract = "Purpose: Rhabdomyosarcomas (RMS) are heterogeneous in their clinical presentation, histology, and cytogenetics. The growth of some RMS cells has been found to be regulated by the tyrosine kinase insulin-like growth factor (IGF) type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of tyrosine kinases and IGF receptors. Collectively, these heterogeneous features suggest that differences exist in the growth regulatory pathways of RMS. The objective of this study is to identify active tyrosine kinase signal transduction pathways in embryonal and alveolar RMS cells. Methods: RMS tumor samples and cell lines representing both embryonal and alveolar histologic subtypes have been analyzed by immunoprecipitation and immunoblotting techniques to characterize phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins. Results: RMS cells can be characterized based on the patterns of phosphotyrosyl proteins, including the phosphorylation status of the catenin-like protein Cas 1 and the signal adapter protein SHC, and the activation of IGF type I receptor signaling cascades including the formation of SHC-GRB2 signal protein complexes and MAP kinase activation. Conclusions: Rhabdomyosarcomas, especially the embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase signal transduction. It will be important to characterize the growth regulatory pathways active in individual RMS tumors before targeting molecular therapies to this malignancy.",
keywords = "Cas 1, Insulin-like growth factor type I receptor, Phosphotyrosyl proteins, Rhabdomyosarcoma, SHC, Signal transduction pathways, Tyrosine kinases",
author = "McManus, {Michael J.} and Hutt, {P. Jesse} and Maihle, {Nita Jane}",
year = "1997",
month = "1",
day = "1",
doi = "10.1097/00043426-199707000-00010",
language = "English (US)",
volume = "19",
pages = "319--326",
journal = "Journal of Pediatric Hematology/Oncology",
issn = "1077-4114",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Phosphotyrosyl proteins in childhood rhabdomyosarcomas

T2 - Phosphorylation of catenins and components of the insulin-like growth factor type I receptor signaling cascade

AU - McManus, Michael J.

AU - Hutt, P. Jesse

AU - Maihle, Nita Jane

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Purpose: Rhabdomyosarcomas (RMS) are heterogeneous in their clinical presentation, histology, and cytogenetics. The growth of some RMS cells has been found to be regulated by the tyrosine kinase insulin-like growth factor (IGF) type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of tyrosine kinases and IGF receptors. Collectively, these heterogeneous features suggest that differences exist in the growth regulatory pathways of RMS. The objective of this study is to identify active tyrosine kinase signal transduction pathways in embryonal and alveolar RMS cells. Methods: RMS tumor samples and cell lines representing both embryonal and alveolar histologic subtypes have been analyzed by immunoprecipitation and immunoblotting techniques to characterize phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins. Results: RMS cells can be characterized based on the patterns of phosphotyrosyl proteins, including the phosphorylation status of the catenin-like protein Cas 1 and the signal adapter protein SHC, and the activation of IGF type I receptor signaling cascades including the formation of SHC-GRB2 signal protein complexes and MAP kinase activation. Conclusions: Rhabdomyosarcomas, especially the embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase signal transduction. It will be important to characterize the growth regulatory pathways active in individual RMS tumors before targeting molecular therapies to this malignancy.

AB - Purpose: Rhabdomyosarcomas (RMS) are heterogeneous in their clinical presentation, histology, and cytogenetics. The growth of some RMS cells has been found to be regulated by the tyrosine kinase insulin-like growth factor (IGF) type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of tyrosine kinases and IGF receptors. Collectively, these heterogeneous features suggest that differences exist in the growth regulatory pathways of RMS. The objective of this study is to identify active tyrosine kinase signal transduction pathways in embryonal and alveolar RMS cells. Methods: RMS tumor samples and cell lines representing both embryonal and alveolar histologic subtypes have been analyzed by immunoprecipitation and immunoblotting techniques to characterize phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins. Results: RMS cells can be characterized based on the patterns of phosphotyrosyl proteins, including the phosphorylation status of the catenin-like protein Cas 1 and the signal adapter protein SHC, and the activation of IGF type I receptor signaling cascades including the formation of SHC-GRB2 signal protein complexes and MAP kinase activation. Conclusions: Rhabdomyosarcomas, especially the embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase signal transduction. It will be important to characterize the growth regulatory pathways active in individual RMS tumors before targeting molecular therapies to this malignancy.

KW - Cas 1

KW - Insulin-like growth factor type I receptor

KW - Phosphotyrosyl proteins

KW - Rhabdomyosarcoma

KW - SHC

KW - Signal transduction pathways

KW - Tyrosine kinases

UR - http://www.scopus.com/inward/record.url?scp=0030725707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030725707&partnerID=8YFLogxK

U2 - 10.1097/00043426-199707000-00010

DO - 10.1097/00043426-199707000-00010

M3 - Article

C2 - 9256831

AN - SCOPUS:0030725707

VL - 19

SP - 319

EP - 326

JO - Journal of Pediatric Hematology/Oncology

JF - Journal of Pediatric Hematology/Oncology

SN - 1077-4114

IS - 4

ER -