v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells

Machida, Kazuya; Matsuda, Satoru; Yamaki, Kenichi; Senga, Takeshi; Thant, Aye Aye; Kurata, Hisashi; Miyazaki, Koichi; Hayashi, Kazuhiko; Okuda, Takayoshi; Kitamura, Toshio; Hayakawa, Tetsuo; Hamaguchi, Michinari

doi:10.1038/sj.onc.1203497

Cited by 21 publications

(24 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, treatment with PP1, a src kinase inhibitor, also increased SIRP␣1 promoter activity. Our results support a previous study showing that overexpression of v-src suppressed SHPS1 (rodent homologue of SIRP) mRNA expression via the Ras-MAPK pathway to promote transformation in fibroblast cells (37) and suggest that src kinase and MAPK pathways may play an important role in regulating SIRP expression at the level of transcription. However, LY294002 and wortmannin, pharmacological inhibitors of the PI3K/Akt pathway, did not affect SIRP␣1 promoter activity (Fig.…”

Section: Transcriptional Regulation Of Sirp␣1 By Egfr Signalingsupporting

confidence: 80%

Transcriptional Regulation of Signal Regulatory Protein α1 Inhibitory Receptors by Epidermal Growth Factor Receptor Signaling

Kapoor¹,

Kapitonov²,

O’Rourke

2004

Cancer Research

View full text Add to dashboard Cite

Signal regulatory protein (SIRP) ␣1 is a membrane glycoprotein and a member of the SIRP receptor family. These transmembrane receptors have been shown to exert negative effects on signal transduction by receptor tyrosine kinases via immunoreceptor tyrosine-based inhibitory motifs in the carboxyl domain. Previous work has demonstrated that SIRPs negatively regulate many signaling pathways leading to reduction in tumor migration, survival, and cell transformation. Thus, modulation of SIRP expression levels or activity could be of great significance in the field of cancer therapy. The aim of the present study was to determine the factors that regulate levels of SIRP␣1 in human glioblastoma cells that frequently overexpress the epidermal growth factor receptor (EGFR) because SIRPs have been shown to negatively regulate EGFR signaling. Northern blot analysis and immunoprecipitation assays showed variable expression levels of endogenous SIRP␣ transcripts in nine well-characterized glioblastoma cell lines. We examined SIRP␣1 regulation in U87MG and U373MG cells in comparison with clonal derivatives that express a truncated form of erbB2, which negatively regulates EGFR signaling by inducing the formation of nonfunctional heterodimeric complexes. Mutant erbB2-expressing cells contained more SIRP␣1 mRNA when compared with the parental cells in presence or absence of serum. Similarly, immunoprecipitation assays showed increased SIRP␣1 protein levels in erbB-inhibited cells when compared with parental cells. Messenger RNA stability assays revealed that the increased mRNA levels in EGFR-inhibited cells were due to an induction of transcription. Consistent with this finding, expression of the erbB2 mutant receptor up-regulated SIRP␣1 promoter activity in all cell lines tested. Interestingly, pharmacological inhibition of the kinase activities of EGFR, erbB2, and src and activation of mitogen-activated protein kinase, but not phosphatidylinositol 3-kinase, significantly up-regulated SIRP␣1 promoter activity. Based on these observations, we hypothesize that down-modulation of EGFR signaling leads to transcriptional up-regulation of the inhibitory SIRP␣1 gene. These data may be important in the application of erbB-inhibitory strategies and for design of therapies for the treatment of glial tumors and other epithelial malignancies.

show abstract

Section: Transcriptional Regulation Of Sirp␣1 By Egfr Signalingsupporting

confidence: 80%

Transcriptional Regulation of Signal Regulatory Protein α1 Inhibitory Receptors by Epidermal Growth Factor Receptor Signaling

Kapoor¹,

Kapitonov²,

O’Rourke

2004

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Expression of SHPS-1 has been shown to be down-regulated in subsets of human leukemic myeloid cells (10), human breast cancer tissue (27), and fibroblasts transformed by various oncogene products (28). Furthermore, forced expression of SHPS-1 suppressed the transformed phenotype of glioblastoma cells (29) as well as inhibited both anchorage-independent growth of v-Src-transformed cells (28) and peritoneal dissemination of these cells in nude mice (27).…”

mentioning

confidence: 99%

“…Furthermore, forced expression of SHPS-1 suppressed the transformed phenotype of glioblastoma cells (29) as well as inhibited both anchorage-independent growth of v-Src-transformed cells (28) and peritoneal dissemination of these cells in nude mice (27). Together, these observations have implicated SHPS-1 in cellular transformation.…”

mentioning

confidence: 99%

Resistance of B16 Melanoma Cells to CD47-induced Negative Regulation of Motility as a Result of Aberrant N-Glycosylation of SHPS-1

Ogura

Noguchi

Murai-Takebe

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…SHP2 binds to several RTK [2,3], adaptor proteins [4][5][6][7][8][9][10][11][12], and SHPS-1 [13]. These interactions are essential for growth factor-or cytokine-induced activation of the multiple receptor-evoked functions.…”

Section: Introductionmentioning

confidence: 99%

Annexin II binds to SHP2 and this interaction is regulated by HSP70 levels

Yoo

Hayman

2007

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The protein tyrosine phosphatase SHP2 is a positive effector of EGFR signaling. To improve our understanding of SHP2's function, we searched for additional binding proteins of SHP2. We found that Annexin II is an SHP2 binding protein. Physical interactions of SHP2 with Annexin II were confirmed in vivo. Furthermore, binding of SHP2 with Annexin II was regulated somewhat by EGF treatment and the extracellular Ca 2+ chelator, EGTA. Previously, we reported that HSP70 levels can influence the binding of SHP2 with EGFR. Interestingly, increased HSP70 levels also inhibited the binding of SHP2 with Annexin II after EGF treatment in vivo. In addition, immunostaining experiments indicated that a fraction of SHP2 and Annexin II co-localized in the cell membrane region after EGF treatment. Our findings indicate that Annexin II is binding partner of SHP2 and the binding of SHP2 with Annexin II is affected by EGF stimulation, extracellular calcium levels and the levels of HSP70.

show abstract

v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells

Cited by 21 publications

References 38 publications

Transcriptional Regulation of Signal Regulatory Protein α1 Inhibitory Receptors by Epidermal Growth Factor Receptor Signaling

Transcriptional Regulation of Signal Regulatory Protein α1 Inhibitory Receptors by Epidermal Growth Factor Receptor Signaling

Resistance of B16 Melanoma Cells to CD47-induced Negative Regulation of Motility as a Result of Aberrant N-Glycosylation of SHPS-1

Annexin II binds to SHP2 and this interaction is regulated by HSP70 levels

Contact Info

Product

Resources

About