EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells
EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells
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DOI：
10.1515/bc.2009.140
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发表时间：
2009-12-01
影响因子：
3.7
通讯作者：
Bruns, Christiane J.
中科院分区：
文献类型：
--
作者：
Camaj, Peter;Seeliger, Hendrik;Bruns, Christiane J.
egf相关蛋白EFEMP1（含egf的纤维蛋白样细胞外基质蛋白1）已被证明能促进人类腺癌的肿瘤生长。为了了解这种作用的机制，研究了用这种蛋白处理后激活的信号转导。我们发现EFEMP1与表皮生长因子（EGF）以竞争的方式结合EGF受体（EGFR），这意味着EFEMP1和EGF在EGFR上具有相同或相邻的结合位点。用纯化的EFEMP1处理胰腺癌细胞可以激活tyr1 -992和tyr1 -1068位点的EGFR自磷酸化，但不会激活tyr1 -1048位点。该信号进一步转导至Akt在Thr-308和p44/p42位点的磷酸化，MAPK（丝裂原活化蛋白激酶）在Thr-202和tyrr -204位点磷酸化。这些下游磷酸化事件可以通过EGFR激酶抑制剂PD 153035进行抑制。在过表达EFEMP1的胰腺癌细胞中，EFEMP1治疗后观察到的信号转导可以促进肿瘤的生长。
The EGF-related protein EFEMP1 (EGF-containing fibulin-like extracellular matrix protein 1) has been shown to promote tumor growth in human adenocarcinoma. To understand the mechanism of this action, the signal transduction activated upon treatment with this protein has been investigated. We show that EFEMP1 binds EGF receptor (EGFR) in a competitive manner relative to epidermal growth factor (EGF), implicating that EFEMP1 and EGF share the same or adjacent binding sites on the EGFR. Treatment of pancreatic carcinoma cells with purified EFEMP1 activates autophosphorylation of EGFR at the positions Tyr-992 and Tyr-1068, but not at the position Tyr-1048. This signal is further transduced to phosphorylation of Akt at position Thr-308 and p44/p42 MAPK (mitogen-activated protein kinase) at positions Thr-202 and Tyr-204. These downstream phosphorylation events can be inhibited by treatment with the EGFR kinase inhibitor PD 153035. The observed signal transduction upon treatment with EFEMP1 can contribute to the enhancement of tumor growth shown in pancreatic carcinoma cells overexpressing EFEMP1.