A computational model on the modulation of mitogen-activated protein kinase (MAPK) and Akt pathways in heregulin-induced ErbB signalling.
نویسندگان
چکیده
ErbB tyrosine kinase receptors mediate mitogenic signal cascade by binding a variety of ligands and recruiting the different cassettes of adaptor proteins. In the present study, we examined heregulin (HRG)-induced signal transduction of ErbB4 receptor and found that the phosphatidylinositol 3'-kinase (PI3K)-Akt pathway negatively regulated the extracellular signal-regulated kinase (ERK) cascade by phosphorylating Raf-1 on Ser(259). As the time-course kinetics of Akt and ERK activities seemed to be transient and complex, we constructed a mathematical simulation model for HRG-induced ErbB4 receptor signalling to explain the dynamics of the regulation mechanism in this signal transduction cascade. The model reflected well the experimental results observed in HRG-induced ErbB4 cells and in other modes of growth hormone-induced cell signalling that involve Raf-Akt cross-talk. The model suggested that HRG signalling is regulated by protein phosphatase 2A as well as Raf-Akt cross-talk, and protein phosphatase 2A modulates the kinase activity in both the PI3K-Akt and MAPK (mitogen-activated protein kinase) pathways.
منابع مشابه
p38 MAPK and PI3K/AKT signalling cascades in Parkinson’s disease
Parkinson's disease (PD) is a chronic neurodegenerative condition which has the second largest incidence rate among all other neurodegenerative disorders barring Alzheimer's disease (AD). Currently there is no cure and researchers continue to probe the therapeutic prospect in cell cultures and animal models of PD. Out of several factors contributing to PD prognosis, the role of p38 MAPKs (mitog...
متن کاملInactivation of mitogen-activated protein kinase signaling pathway reduces caspase-14 expression in impaired keratinocytes
Objective(s):Several investigations have revealed that caspase-14 is responsible for the epidermal differentiation and cornification, as well as the regulation of moisturizing effect. However, the precise regulation mechanism is still not clear. This study was aimed to investigate the expression of caspase-14 in filaggrin-deficient normal human epidermal keratinocytes (NHEKs) and to explore the...
متن کاملAnti-inflammatory Effects of Oxymatrine Through Inhibition of Nuclear Factor–kappa B and Mitogen-activated Protein Kinase Activation in Lipopolysaccharide-induced BV2 Microglia Cells
Oxymatrine, a potent monosomic alkaloid extracted from Chinese herb Sophora japonica (Sophora flavescens Ait.). possesses anti-inflammatory activittyes. This study was designed to investigate the effects of oxymatrine on nuclear factor–kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)-dependent inflammatory responses in lipopolysaccharide (LPS)-activated microglia. In this paper, BV2...
متن کاملBreast tumor kinase (protein tyrosine kinase 6) regulates heregulin-induced activation of ERK5 and p38 MAP kinases in breast cancer cells.
Total tyrosine kinase activity is often elevated in both cytosolic and membrane fractions of malignant breast tissue and correlates with a decrease in disease-free survival. Breast tumor kinase (Brk; protein tyrosine kinase 6) is a soluble tyrosine kinase that was cloned from a metastatic breast tumor and found to be overexpressed in a majority of breast tumors. Herein, we show that Brk is over...
متن کاملAnti-inflammatory Effects of Oxymatrine Through Inhibition of Nuclear Factor–kappa B and Mitogen-activated Protein Kinase Activation in Lipopolysaccharide-induced BV2 Microglia Cells
Oxymatrine, a potent monosomic alkaloid extracted from Chinese herb Sophora japonica (Sophora flavescens Ait.). possesses anti-inflammatory activittyes. This study was designed to investigate the effects of oxymatrine on nuclear factor–kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)-dependent inflammatory responses in lipopolysaccharide (LPS)-activated microglia. In this paper, BV2...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Biochemical journal
دوره 373 Pt 2 شماره
صفحات -
تاریخ انتشار 2003