Journal
EUROPEAN JOURNAL OF BIOCHEMISTRY
Volume 267, Issue 6, Pages 1583-1588Publisher
WILEY-BLACKWELL
DOI: 10.1046/j.1432-1327.2000.01197.x
Keywords
signal transduction; protein phosphorylation; MAPK cascades; bistability; sustained oscillations
Categories
Funding
- NIAAA NIH HHS [AA07215, AA11689, AA01786] Funding Source: Medline
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R03AA011689] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Functional organization of signal transduction into protein phosphorylation cascades, such as the mitogen-activated protein kinase (MAPK) cascades, greatly enhances the sensitivity of cellular targets to external stimuli. The sensitivity increases multiplicatively with the number of cascade levels, so that a tiny change in a stimulus results in a large change in the response, the phenomenon referred to as ultrasensitivity. In a variety of cell types, the MAPK cascades are imbedded in long feedback loops, positive or negative, depending on whether the terminal kinase stimulates or inhibits the activation of the initial level. Here we demonstrate that a negative feedback loop combined with intrinsic ultrasensitivity of the MAPK cascade can bring about sustained oscillations in MAPK phosphorylation. Based on recent kinetic data on the MAPK cascades, we predict that the period of oscillations can range from minutes to hours. The phosphorylation level can vary between the base level and almost 100% of the total protein. The oscillations of the phosphorylation cascades and slow protein diffusion in the cytoplasm can lead to intracellular waves of phospho-proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available