Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells.

Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells. Research Abstract Details 

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Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells. Abstract Text:

Takashi Nagashima,Tetsuo Maruyama,Hiroshi Uchida,Takashi Kajitani,Toru Arase,Masanori Ono,Hideyuki Oda,Maki Kagami,Hirotaka Masuda,Sayaka Nishikawa,Hironori Asada,Yasunori Yoshimura,

Progesterone induces decidual transformation of estrogen-primed human endometrial stromal cells (hESCs), critical for implantation and maintenance of pregnancy, through activation of many signaling pathways involving protein kinase A and signal transducer and activator of transcription (STAT)-5. We have previously shown that kinase activation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) kinase is closely associated with decidualization and that SRC is indispensable for maximal decidualization in mice. To address whether SRC kinase activity is essential for decidualization in humans, hESCs were infected with adenoviruses carrying enhanced green fluorescent protein alone (Ad-EGFP), a kinase-inactive dominant-negative mutant (Ad-SRC/K295R), or an inactive autophosphorylation site mutant (Ad-SRC/Y416F). The cells were cultured in the presence of estradiol and progesterone (EP) to induce decidualization and subjected to RT-PCR, immunoblot, and ELISA analyses. Ad-EGFP-infected hESCs exhibited decidual transformation and up-regulation of decidualization markers including IGF binding protein 1 and prolactin in response to 12-d treatment with EP. In contrast, hESCs infected with Ad-SRC/K295R remained morphologically fibroblastoid without production of IGF binding protein 1 and prolactin even after EP treatment. Ad-SRC/Y416F displayed similar but less inhibitory effects on decidualization, compared with Ad-SRC/K295R. During decidualization, STAT5 was phosphorylated on tyrosine 694, a well-known SRC phosphorylation site. Phosphorylation was markedly attenuated by Ad-SRC/K295R but not Ad-EGFP. These results indicate that the SRC-STAT5 pathway is essential for decidualization of hESCs.

Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells. Publishing Authors By Initials

T Nagashima,T Maruyama,H Uchida,T Kajitani,T Arase,M Ono,H Oda,M Kagami,H Masuda,S Nishikawa,H Asada,Y Yoshimura,

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Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Endocrinology

VOLUME: 149

Page Numbers: 1227-34

Journal Abbreviation: Endocrinology

ISSN: 0013-7227

DAY: 6

MONTH: 12

YEAR: 2007

Activation of SRC kinase and phosphorylation of signal transducer and activator of transcription-5 are required for decidual transformation of human endometrial stromal cells. Information

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LANGUAGE: eng

NlmUniqueID: 375040

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AFFILIATION: Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan. tetsuo@sc.itc.keio.ac.jp.

Country: United States

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MEDLINETA: Endocrinology

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