Inhibition of Ca2+/calmodulin-dependent protein kinase or epidermal growth factor receptor tyrosine kinase abolishes lysophosphatidic acid-mediated DNA-synthesis in human myometrial smooth muscle cells.


:Human myometrial smooth muscle cells (SMCs) were used to evaluate the proliferative activity of lysophosphatidic acid (LPA). This study specifically focuses on the role of Ca(2+)/calmodulin-dependent protein (CaM) kinase and epidermal growth factor (EGF) receptor tyrosine kinase. Myometrial SMCs were cultured from biopsies taken at Cesarean sections. The expression of LPA receptors was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and DNA-synthesis was measured by [3H]thymidine incorporation. LPA(1), LPA(2), and LPA(3)receptor subtypes were detected in the SMCs using RT-PCR. KN-62, an inhibitor of CaM kinase, and Tyrphostin AG 1478, an inhibitor of EGF receptor tyrosine kinase, dose-dependently decreased LPA-stimulated [3H]thymidine incorporation. Furthermore, BB-3103, an inhibitor of matrix metalloproteinases (MMPs), also reduced DNA-synthesis induced by LPA in these cells. The results show, for the first time, that human myometrial SMCs express all three known LPA receptor subtypes. Growth stimulatory effects of LPA on myometrial SMCs seems to be mediated by several pathways, where transactivation of EGF receptors through MMPs appears to be of importance. Furthermore, CaM kinase activity may be critical for LPA signaling since inhibition of CaM kinase totally abolish the proliferative effect of LPA.


Cell Biol Int


Nilsson UK,Svensson SP





Has Abstract


2003-01-01 00:00:00














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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Karalyan ZA,Djaghatspanyan NG,Gasparyan MH,Hakobyan LA,Abroyan LO,Magakyan YH,Ter-Pogossyan ZR,Kamalyan LA,Avagyan VY,Karalova EM

    更新日期:2003-01-01 00:00:00

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Zhu N,Ruan J,Yang X,Huang Y,Jiang Y,Wang Y,Cai D,Geng Y,Fang M

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Dinçer T,Boz Er AB,Er İ,Toraman B,Yildiz G,Kalay E

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Shen E,Zhao K,Wu C,Yang B

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Henics T,Nagy E,Rigby WF

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    journal_title:Cell biology international

    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Kamei H

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    journal_title:Cell biology international

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Cell biology international

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    authors: Dongkyun K,Jinsoo S,Jin EJ

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Sabaneyeva E,Tao W,Verbelen JP

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    pub_type: 杂志文章


    authors: Yemets A,Radchuk V,Bayer O,Bayer G,Pakhomov A,Vance Baird W,Blume YB

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    journal_title:Cell biology international

    pub_type: 杂志文章


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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Wang H,Huang Y

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Maroni P,Bendinelli P,Piccoletti R

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    journal_title:Cell biology international

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Moizhess TG,Vasiliev JM

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Lertworasirikul T,Bunyaratvej A,Kubota F

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Awan SJ,Baig MT,Yaqub F,Tayyeb A,Ali G

    更新日期:2017-01-01 00:00:00

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Evans PJ

    更新日期:1999-01-01 00:00:00

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Hu JL,Xiao L,Li ZY,Wang Q,Chang Y,Jin Y

    更新日期:2013-06-01 00:00:00

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    journal_title:Cell biology international

    pub_type: 杂志文章


    authors: Cooper S,Shedden K,Vu-Phan D

    更新日期:2009-01-01 00:00:00