The way in which the proteins in a cell transmit signals to one another is hugely important for controlling cell division, cell migration and even cell death. If this process goes wrong, it can lead to the onset of diseases such as cancer.
This is the first part of a series of animations exploring cell signalling, this time focusing on kinases and phosphorylations. Within a cell, phosphorylations are a major way in which proteins can transmit chemical signals to one another. In this video, we're exploring what you need in order to perform a phosphorylation, how it works and what happens when proteins are phosphorylated.
Below are some references of seminal papers in the field. Early sequence alignments of ~100 protein kinases showed remarkable conservation of particular amino acid motifs (1), and these same residues were found to be important to activity when scanning mutagenesis experiments tested activity after sequentially mutating kinase residues (2). While these conserved motifs are far apart in the amino acid sequence, the first structures of a kinase (3, 4) showed that they are all close to ATP and the substrate in three dimensional space. The original list of kinases was massively expanded to 518 members using data gathered from the Human Genome Project (5).
References:
(1) Hanks, S.K., Quinn, A.M., and Hunter, T. (1988) ‘The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains’. Science (New York, NY) 241 (4861), 42-52
(2) Gibbs, C.S. and Zoller, M.J. (1991) ‘Rational Scanning Mutagenesis of a Protein Kinase Identifies Functional Regions Involved in Catalysis and Substrate Interactions.’. The Journal of biological chemistry 266 (14), 8923-8931
(3) Knighton, D.R., Zheng, J.H., Eyck, Ten, L.F., Ashford, V.A., Xuong, N.H., Taylor, S.S., and Sowadski, J.M. (1991a) ‘Crystal Structure of the Catalytic Subunit of Cyclic Adenosine Monophosphate-Dependent Protein Kinase.’. Science (New York, NY) 253 (5018), 407-414
(4) Knighton, D.R., Zheng, J.H., Eyck, Ten, L.F., Xuong, N.H., Taylor, S.S., and Sowadski, J.M. (1991b) ‘Structure of a Peptide Inhibitor Bound to the Catalytic Subunit of Cyclic Adenosine Monophosphate-Dependent Protein Kinase’. Science (New York, NY) 253 (5018), 414-420
(5) Manning, G., Whyte, D.B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002b) ‘The Protein Kinase Complement of the Human Genome.’. Science (New York, NY) 298 (5600), 1912-1934
20 май 2015
