9318124 Cooper Biological systems are, in general, very resourceful in responding to external signals. We have identified such a response in BC3H-1 myocytes, a mouse muscle cell line. These cells are used in research because they respond to insulin to increase glucose uptake. In this case, the myocytes rapidly switch the types of proteins they synthesize so that they can enhance glucose uptake in response to insulin. The protein being investigated is protein kinase C beta. This enzyme phosphorylates or regulates other enzymes to enhance or inhibit their function. It is a component of the glucose transport system in myocytes and its activation is required for the stimulation of glucose uptake. Protein kinase C beta is interesting because two forms of the enzyme can be expressed by cells due to alternative splicing of its precursor RNA. Alternative splicing of protein kinase C beta leads to differences in the C-terminal end of the protein that is synthesized. This difference means that two different proteins can be expressed from one primary transcript of RNA. The cell can respond to hormones such as insulin which control the alternative splicing very quickly. In this case, protein kinase C beta II is more effective than protein kinase beta I in enhancing insulin effects on glucose transport. The actual factors controlling alternative splicing of PKC beta are unknown. We want to identify these factors and determine how insulin can regulate alternative splicing so that cells can alter their physiological responses to hormones such as insulin. ***
