Control of Alternative Splicing

The formation of the exon-recognition complexes is subject to numerous controls. The first level of control is the variation of regulatory factor concentrations that often differ between cell types (Hanamura et al. 1998). In addition to this regulation, the activity of splicing regulatory proteins is regulated by post-translational modifications, especially reversible phosphorylation. Phosphorylation influences the binding affinity between splicing regulatory proteins and can therefore control the formation of exon-recognition complexes. It is not fully understood what controls the phosphorylation of splicing factors, but numerous studies indicate that well-established signaling routes, such as mitogen activated protein (MAP)-kinase, Ca2+-dependent kinase, and cyclic adenosine monophosphate (cAMP)-dependent pathways are involved. This model explains why numerous cellular stimuli, such as receptor activation or membrane depolarization can influence splice site selection. This paradigm also implies that tissue- and cell-specific differences in alternative splicing could be due to different signals that cells receive (reviewed in Stamm 2008; Shin and Manley 2004; Stamm 2002).

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Being addicted to drugs is a complicated matter condition that's been specified as a disorder that evidences in the obsessional thinking about and utilization of drugs. It's a matter that might continue to get worse and become disastrous and deadly if left untreated.

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