Multiple pathway signal transduction by the cAMP-dependent protein kinase.
Since its discovery a quarter century ago, the cAMP-dependent protein kinase has been a central model for study of the mode of transduction of second messenger signals; more than 300 protein kinases are now known to play keys roles in cellular control. Multiple cellular events are initiated by the activation of the cAMP-dependent protein kinase and correlated with these events has been the identification of a broad spectrum of protein substrates. From model substrates and inhibitors an excellent understanding has been obtained of the "optimum" sequence for protein phosphorylation by the cAMP-dependent protein kinases, and now, from pioneering crystal structure studies, we are beginning to understand exactly how an optimum substrate can interact with and be efficiently phosphorylated by the kinase. The next important step is for us to understand the full sequence of events that occurs within the cell upon activation of the protein kinase, and it is abundantly evident that this is indeed a complex process. It is not sufficient to simply know which proteins are phosphorylated but it is critical that we understand the dynamics of the events surrounding the phosphorylation of multiple proteins, what factors dictate those dynamics, and what might happen when the sequence of events is perturbed. This review focuses on the first simple question that must be addressed, namely, how might proteins vary as substrates for the cAMP-dependent protein kinase and what ramifications might such variations have for the consequential events within the cell?
Walsh
D A
DA
Department of Biological Chemistry, School of Medicine, University of California, Davis 95616.
Van Patten
S M
SM
D000595:Amino Acid Sequence; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D015398:Signal Transduction; D013379:Substrate Specificity
D017868:Cyclic AMP-Dependent Protein Kinases