Kinase Ck1¦Á Tnf / Nf-kappa B Signal Transduction Pathway Through The Phosphorylation Of Protein Rip

Casein kinase 1 (CK1) was one of the pioneer protein kinase activities that have been isolated, and was named for its character that strongly phosporylating casein. CK1 have been found in all eukaryotes and it forms a separate group within the superfamily of eukaryotic protein kinase. Seven genes encoding α,β,γ1, γ2, γ3, δ and ε isoforms of CK1 have been characterized in mammals and vertebrates, and some of these genes could produce several proteins through alternative splicing. CK1 isoforms have been shown to phosphorylate hundreds of proteins from all cell compartments and the number of its substrates is still increasing. The diversity of CK1 substrates including various functional groups of intracellular proteins, indicate that CK1 is involved in the regulation of many different cellular processes. CK1 has been implicated in a wide range of cellular functions, including vesicular trafficking, cell cycle progression, cytokinesis apoptosis and p53 regulation. Within recent years increased evidences also suggested that CK1 play an important role in neurodegenerative diseases and in the progression of some kinds of cancers.CK1α has a calculated molecular weight of 37 KD, and beyond the catalytic domain, the kinase possesses a NH2 and carboxyl terminus which are too short to form a domain. RT-PCR and Western blotting data indicate that it is expressed approximately equally in all tissues and detected in all cellular compartments. Functionally, it is involved in the regulation of many signal pathwaysincluding Wnt, Hedgehog, NF-AT death-receptor induced apoptosis, and so on..Tumor necrosis factor a (TNFα), which is a cytokine, induces an extraordinary wide variety ofbiological responses including apoptosis as well as immune regulation, inflammation cell proliferation and differentiation. It has been implicated in the pathogenesis of a wide spectrum of human diseases, such as sepsis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases. TNF exerts its diverse biological properties by binding to and activating two distinct cell surface receptors, TNFR1 and TNFR2, and TNFR1 is responsible for the major cellular activity. It is well known that...