CAM KINASE - A MODEL FOR ITS ACTIVATION AND DYNAMICS
CAM KINASE - A MODEL FOR ITS ACTIVATION AND DYNAMICS
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DOI:
10.1006/jtbi.1994.1231
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发表时间:
1994-12-07
影响因子:
2
通讯作者:
SCHULMAN, H
中科院分区:
文献类型:
--
作者:
MICHELSON, S;SCHULMAN, H
Multifunctional calmodulin kinase (CaM kinase) is an enzyme which transduces fluctuations of intracellular calcium ion concentrations into kinase activity. The enzyme phosphorylates a variety of target proteins. Activation of CaM kinase requires the formation of a calcium-calmodulin complex and binding by the complex to one of ten identical subunits of the holoenzyme. The CaM kinase enzyme is a ring. Each subunit in the ring traverses a path between five distinct activation states. Transitions between activation states depend upon the dynamic calcium-calmodulin complex levels, binding and release of the complex to the subunits' activation sites, and the activation status of the right-hand neighboring subunit in the ring. The dynamic distribution of a given subunit's state is modeled using a conditional (conditioned upon the neighbor's status), finite state, non-homogeneous Markov process. A simulation package for enzyme activation has been developed, and initial studies with one calcium spike, low-frequency-low-amplitude sinusoids, and spike trains are presented. The capability of the CaM kinase molecule to act as an information processor, translating short-term calcium fluctuations into long-term activation (i.e. ''memory'') is discussed.