CAM KINASE - A MODEL FOR ITS ACTIVATION AND DYNAMICS

Multifunctional calmodulin kinase (CaM kinase) is an enzyme which tran sduces fluctuations of intracellular calcium ion concentrations into k inase activity. The enzyme phosphorylates a variety of target proteins . Activation of CaM kinase requires the formation of a calcium-calmodu lin complex and binding by the complex to one of ten identical subunit s of the holoenzyme. The CaM kinase enzyme is a ring. Each subunit in the ring traverses a path between five distinct activation states. Tra nsitions between activation states depend upon the dynamic calcium-cal modulin complex levels, binding and release of the complex to the subu nits' activation sites, and the activation status of the right-hand ne ighboring subunit in the ring. The dynamic distribution of a given sub unit's state is modeled using a conditional (conditioned upon the neig hbor's status), finite state, non-homogeneous Markov process. A simula tion package for enzyme activation has been developed, and initial stu dies with one calcium spike, low-frequency-low-amplitude sinusoids, an d spike trains are presented. The capability of the CaM kinase molecul e to act as an information processor, translating short-term calcium f luctuations into long-term activation (i.e. ''memory'') is discussed.