Simulation of crosstalk between small GTPase RhoA and EGFR-ERK signaling pathway via MEKK1

نویسندگان

  • Hu Li
  • Choong Yong Ung
  • Xiao Hua Ma
  • Bao Wen Li
  • Boon Chuan Low
  • Zhi-Wei Cao
  • Yu Zong Chen
چکیده

MOTIVATION Small GTPase RhoA regulates cell-cycle progression via several mechanisms. Apart from its actions via ROCK, RhoA has recently been found to activate a scaffold protein MEKK1 known to promote ERK activation. We examined whether RhoA can substantially affect ERK activity via this MEKK1-mediated crosstalk between RhoA and EGFR-ERK pathway. By extending the published EGFR-ERK simulation models represented by ordinary differential equations, we developed a simulation model that includes this crosstalk, which was validated with a number of experimental findings and published simulation results. RESULTS Our simulation suggested that, via this crosstalk, RhoA elevation substantially prolonged duration of ERK activation at both normal and reduced Ras levels. Our model suggests ERK may be activated in the absence of Ras. When Ras is overexpressed, RhoA elevation significantly prolongs duration of ERK activation but reduces the amount of active ERK partly due to competitive binding between ERK and RhoA to MEKK1. Our results indicated possible roles of RhoA in affecting ERK activities via MEKK1-mediated crosstalk, which seems to be supported by indications from several experimental studies that may also implicate the collective regulation of cell fate and progression of cancer and other diseases.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

P-111: EGFR, ERK, MEK Genes Expression Level in Cumulus Cells of PCOS Women Compared with Healthy Women

Background Poly cystic ovarian syndrome (PCOS) is known as a common endocrine disorder in women at reproductive ages and may cause developmental abnormality in oocyte. ERK has found as a regulator protein of Gap junctions (GJ) function and the level of exchanges between two neighbors cells, for example oocyte and surrounding cumulus cells (CCs) in the mammalian ovary. Such exchange is essential...

متن کامل

Central role of the exchange factor GEF-H1 in TNF-α–induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells

Transactivation of the epidermal growth factor receptor (EGFR) by tumor necrosis factor-α (TNF-α) is a key step in mediating RhoA activation and cytoskeleton and junction remodeling in the tubular epithelium. In this study we explore the mechanisms underlying TNF-α-induced EGFR activation. We show that TNF-α stimulates the TNF-α convertase enzyme (TACE/a disintegrin and metalloproteinase-17), l...

متن کامل

MiR-96 induced non-small-cell lung cancer progression through competing endogenous RNA network and affecting EGFR signaling pathway

Objective(s): Non-small cell lung cancer (NSCLC) has become a serious global health problem in the 21st century, and tumor proliferation and metastasis are the leading causes of death in patients  with lung cancer. The present study aimed to verify the function of miR-96 and miR-96 in relation to competing with endogenous RNA regulatory network in NSCLC progression inc...

متن کامل

Nitric oxide-induced inhibition of smooth muscle cell proliferation involves S-nitrosation and inactivation of RhoA.

Nitric oxide (NO) acts as a vasoregulatory molecule that inhibits vascular smooth muscle cell (SMC) proliferation. Studies have illustrated that NO inhibits SMC proliferation via the extracellular signal-regulated kinase (ERK) pathway, leading to increased protein levels of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). The ERK pathway can be pro- or antiproliferative, and it has been de...

متن کامل

ذخیره 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 نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Bioinformatics

دوره 25 3  شماره 

صفحات  -

تاریخ انتشار 2009