EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells
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Peter Camaj
Abstract
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.
©2009 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Reviews
- Chemokines in tumor-associated angiogenesis
- The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver
- The mechanism of ATP-dependent RNA unwinding by DEAD box proteins
- Protein Structure and Function
- Crystal structure of 4-hydroxybutyrate CoA-transferase from Clostridium aminobutyricum
- Factors regulating tachyphylaxis triggered by N-terminal-modified angiotensin II analogs
- Cancer Osaka thyroid (Cot) phosphorylates Polo-like kinase (PLK1) at Ser137 but not at Thr210
- Coagulation factor XIII variants with altered thrombin activation rates
- Cell Biology and Signaling
- Stimulation of fibroblast proliferation by the plant cysteine protease CMS2MS2 is independent of its proteolytic activity and requires ERK activation
- EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells
- Identification of collagen IV derived danger/alarm signals in insect immunity by nanoLC-FTICR MS
- Proteolysis
- Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by distinct proteolytic cleavage
- Acknowledgment
- Acknowledgment
- Contents Volume 390, 2009
- Contents Biological Chemistry, Volume 390, 2009
- Author Index
- Author Index
- Subject Index
- Subject Index
Artikel in diesem Heft
- Reviews
- Chemokines in tumor-associated angiogenesis
- The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver
- The mechanism of ATP-dependent RNA unwinding by DEAD box proteins
- Protein Structure and Function
- Crystal structure of 4-hydroxybutyrate CoA-transferase from Clostridium aminobutyricum
- Factors regulating tachyphylaxis triggered by N-terminal-modified angiotensin II analogs
- Cancer Osaka thyroid (Cot) phosphorylates Polo-like kinase (PLK1) at Ser137 but not at Thr210
- Coagulation factor XIII variants with altered thrombin activation rates
- Cell Biology and Signaling
- Stimulation of fibroblast proliferation by the plant cysteine protease CMS2MS2 is independent of its proteolytic activity and requires ERK activation
- EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells
- Identification of collagen IV derived danger/alarm signals in insect immunity by nanoLC-FTICR MS
- Proteolysis
- Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by distinct proteolytic cleavage
- Acknowledgment
- Acknowledgment
- Contents Volume 390, 2009
- Contents Biological Chemistry, Volume 390, 2009
- Author Index
- Author Index
- Subject Index
- Subject Index
