Novel participation of transglutaminase-2 through c-Jun N-terminal kinase activation in sphingosylphosphorylcholine-induced keratin reorganization of PANC-1 cells

详细信息    查看全文

• 作者：Mi Kyung  ; Park^a ; Hye Ja  ; Lee^a ; Jennifer  ; Shin^b ; Minsoo  ; Noh^c ; Soo Youl  ; Kim^d ; Chang Hoon  ; Lee^a ;   ; ^{uatheone@dongguk.edu}
• 关键词：Sphingosylphosphorylcholine ; Transglutaminase-2 ; Keratin-8 phosphorylation and reorganization ; c-Jun N-terminal kinase ; Migration
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：1811
• 期：12
• 页码：1021-1029
• 全文大小：1012 K

文摘

Sphingosylphosphorylcholine (SPC) is found at increased levels in the malignant ascites of tumor patients and induces perinuclear reorganization of keratin 8 (K8) filaments that contribute to the viscoelasticity of metastatic cancer cells. In this study, we investigated the role and molecular mechanisms of Tgase-2 in SPC-induced K8 phosphorylation and perinuclear reorganization in PANC-1 cells (PAN_WT), and in PANC-1 cells that stably expressed shTgase-2 or Tgase-2 (PAN_shTg2 and PAN_Tg2). SPC induces the expression of Tgase-2 in a time- and dose-dependent manner. Gene silencing of Tgase-2 or cystamine suppressed the SPC-induced phosphorylation and perinuclear reorganization of K8 and suppressed the SPC-induced migration of PANC-1 cells. An inhibitor of c-Jun N-terminal kinase (JNK), SP600125, suppressed the SPC-induced phosphorylation of serine 431 in K8 and keratin reorganization. Next, we examined the effect of Tgase-2 on JNK activation of serine 431 phosphorylation in K8. Tgase-2 gene silencing suppressed the expression of active form JNK (pJNK). Constitutive or tetracyclin-induced conditional expression of Tgase-2 increased the levels of pJNK. Tgase-2 was coimmunoprecipitated with K8 and JNK. In addition, K8 was coimmunoprecipitated with Tgase-2 and JNK. JNK was also coimmunoprecipitated with K8 and Tgase-2. Overall, these results suggest that Tgase-2 is involved in SPC-induced phosphorylation and perinuclear reorganization of K8 by activating JNK and forming a triple complex with K8 and JNK. Therefore, SPC-induced Tgase-2 might be a new target for modulating keratin reorganization, metastasis of cancer cells and JNK activation.