RRC ID 68502
Author Miyake I, Hakomori Y, Shinohara A, Gamou T, Saito M, Iwamatsu A, Sakai R.
Title Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines.
Journal Oncogene
Abstract Shc family of docking proteins, ShcA, ShcB and ShcC, play roles in cellular signal transduction by binding to phosphotyrosine residues of various activated receptor tyrosine kinases. Both ShcB and ShcC proteins are selectively expressed in the neural system of adult mouse tissues. In most of neuroblastoma cells, obvious tyrosine phosphorylation of ShcC was observed, whereas expression of ShcB was considerably low. Phosphoproteins associated with hyperphosphorylated ShcC were purified from neuroblastoma cell lines, and identified by mass-spectrometry. Anaplastic lymphoma kinase (ALK), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the PTB domain of ShcC in three neuroblastoma cells. In vitro kinase assay revealed that ShcC is a potent substrate of the activated ALK kinase. The ALK gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the ALK kinase, which results in hyperphosphorylation of ShcC. Constitutive activation of ALK appeared to interfere with signals from other receptor tyrosine kinases. ALK-ShcC signal activation, possibly caused by co-amplification with the N-myc gene, might give additional effects on malignant tumor progression of neuroblastoma.
Volume 21(38)
Pages 5823-34
Published 2002-8-29
DOI 10.1038/sj.onc.1205735
PMID 12185581
MeSH Adult Anaplastic Lymphoma Kinase Animals Chromatography, Affinity / methods Enzyme Activation Humans Infant Male Mice Mice, Nude Nerve Tissue Proteins / metabolism* Nervous System Neoplasms / metabolism Neuroblastoma / genetics Neuroblastoma / metabolism* Neuropeptides* Phosphoproteins / isolation & purification Phosphoproteins / metabolism Phosphorylation Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism* Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism* Shc Signaling Adaptor Proteins Signal Transduction Src Homology 2 Domain-Containing, Transforming Protein 3 Tumor Cells, Cultured Tyrosine / metabolism
IF 7.971
Human and Animal Cells KU-YS(RCB1318) SK-N-SH(RCB0426) TNB1(RCB0481) KP-N-NS(RCB0687)