Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215

Ratna K. Vadlamudi; Aysegul A. Sahin; Liana Adam; Rui An Wang; Rakesh Kumar

doi:10.1016/S0014-5793(03)00404-6

Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215

Ratna K. Vadlamudi, Aysegul A. Sahin, Liana Adam, Rui An Wang, Rakesh Kumar

Research output: Contribution to journal › Article › peer-review

75 Scopus citations

Abstract

To elucidate the molecular mechanisms by which human epidermal growth factor receptor/heregulin (HER2/HRG) influence the migratory potential of breast cancer cells, we have used phospho-specific antibodies against c-Src kinase and focal adhesion kinase (FAK). This study establishes that HER2/HRG signaling selectively upregulates Tyr phosphorylation of c-Src at Tyr-215 located within the SH2 domain, increases c-Src kinase activity and selectively upregulates Tyr phosphorylation of FAK at Tyr-861. HER2-overexpressing tumors showed increased levels of c-Src phosphorylation at Tyr-215. These findings suggest that HER2/HRG influence metastasis of breast cancer cells through a novel signaling pathway involving phosphorylation of FAK tyrosine 861 via activation of c-Src tyrosine 215.

Original language	English (US)
Pages (from-to)	76-80
Number of pages	5
Journal	FEBS Letters
Volume	543
Issue number	1-3
DOIs	https://doi.org/10.1016/S0014-5793(03)00404-6
State	Published - May 22 2003
Externally published	Yes

Keywords

Cytoplasmic tyrosine kinase
Growth factor signaling
Receptor tyrosine kinase

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(03)00404-6

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title = "Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215",

abstract = "To elucidate the molecular mechanisms by which human epidermal growth factor receptor/heregulin (HER2/HRG) influence the migratory potential of breast cancer cells, we have used phospho-specific antibodies against c-Src kinase and focal adhesion kinase (FAK). This study establishes that HER2/HRG signaling selectively upregulates Tyr phosphorylation of c-Src at Tyr-215 located within the SH2 domain, increases c-Src kinase activity and selectively upregulates Tyr phosphorylation of FAK at Tyr-861. HER2-overexpressing tumors showed increased levels of c-Src phosphorylation at Tyr-215. These findings suggest that HER2/HRG influence metastasis of breast cancer cells through a novel signaling pathway involving phosphorylation of FAK tyrosine 861 via activation of c-Src tyrosine 215.",

keywords = "Cytoplasmic tyrosine kinase, Growth factor signaling, Receptor tyrosine kinase",

author = "Vadlamudi, {Ratna K.} and Sahin, {Aysegul A.} and Liana Adam and Wang, {Rui An} and Rakesh Kumar",

note = "Funding Information: Supported in part by the Department of Defense Breast Cancer Research Program Grant BC996185 (R.K.V.) and NIH Grant CA90970 (R.K.).",

year = "2003",

month = may,

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doi = "10.1016/S0014-5793(03)00404-6",

language = "English (US)",

volume = "543",

pages = "76--80",

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T1 - Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215

AU - Vadlamudi, Ratna K.

AU - Sahin, Aysegul A.

AU - Adam, Liana

AU - Wang, Rui An

AU - Kumar, Rakesh

N1 - Funding Information: Supported in part by the Department of Defense Breast Cancer Research Program Grant BC996185 (R.K.V.) and NIH Grant CA90970 (R.K.).

PY - 2003/5/22

Y1 - 2003/5/22

N2 - To elucidate the molecular mechanisms by which human epidermal growth factor receptor/heregulin (HER2/HRG) influence the migratory potential of breast cancer cells, we have used phospho-specific antibodies against c-Src kinase and focal adhesion kinase (FAK). This study establishes that HER2/HRG signaling selectively upregulates Tyr phosphorylation of c-Src at Tyr-215 located within the SH2 domain, increases c-Src kinase activity and selectively upregulates Tyr phosphorylation of FAK at Tyr-861. HER2-overexpressing tumors showed increased levels of c-Src phosphorylation at Tyr-215. These findings suggest that HER2/HRG influence metastasis of breast cancer cells through a novel signaling pathway involving phosphorylation of FAK tyrosine 861 via activation of c-Src tyrosine 215.

AB - To elucidate the molecular mechanisms by which human epidermal growth factor receptor/heregulin (HER2/HRG) influence the migratory potential of breast cancer cells, we have used phospho-specific antibodies against c-Src kinase and focal adhesion kinase (FAK). This study establishes that HER2/HRG signaling selectively upregulates Tyr phosphorylation of c-Src at Tyr-215 located within the SH2 domain, increases c-Src kinase activity and selectively upregulates Tyr phosphorylation of FAK at Tyr-861. HER2-overexpressing tumors showed increased levels of c-Src phosphorylation at Tyr-215. These findings suggest that HER2/HRG influence metastasis of breast cancer cells through a novel signaling pathway involving phosphorylation of FAK tyrosine 861 via activation of c-Src tyrosine 215.

KW - Cytoplasmic tyrosine kinase

KW - Growth factor signaling

KW - Receptor tyrosine kinase

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U2 - 10.1016/S0014-5793(03)00404-6

DO - 10.1016/S0014-5793(03)00404-6

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AN - SCOPUS:0038393116

SN - 0014-5793

VL - 543

SP - 76

EP - 80

JO - FEBS Letters

JF - FEBS Letters

IS - 1-3

ER -

Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215

Abstract

Keywords

ASJC Scopus subject areas

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