Protein kinases sequences

Cyclin-Cdks were appropriately named the cell cycle s engines . The cyclin-dependent protein kinases (Cdks) are soluble serine/threonine kinases of 34-40 kDa. The Cdks share with other serine/threonine protein kinases sequence similarities, including a subset of residues that is essential for catalytic activity. Cdks contribute the catalytic subunit, whereas the regulatory subunit is contributed by a cyclin. Cyclins control the kinase activity, determine the substrate specificity and the subcellular location of Cdks. Each of these processes is a potential site of regulation. The major substrates of the Cdks are proteins regulating gene transcription. Cdks can be controlled in three major ways ... 

It has been proposed that hormones and neurotransmitters as well as other types of regulatory agents control physiological processes by means of protein phosphorylation (Greengard, 1975, 1976). Some of the protein phosphorylation occurs as a consequence of a hormone receptor-adenylate cyclase-cAMP-protein kinase sequence of action. In other cases, different cyclic nucleotides may replace cAMP, while with cyclic nucleotide-independent protein kinases, other signal molecules. 

Protein Kinase Class Target Sequence Activators... 

Apelin receptors activate several signalling pathways including coupling through inhibitory G-proteins (G ) and Ras-independent activation of extracellular-regulated kinases (ERKs) via protein kinase C (PKC). The apelin receptor is one of number of G-protein-coupled receptors that can act as an alternative coreceptor for entry into cells of HIV and simian immunodeficiency vims (SIV) strains in human U87 cells expressing CD4 in vitro. Apelin peptides blocks entry of HIV but display different potencies, with apelin-36 being more effective than shorter sequences [3]. 

Protein Kinase C. Figure 1 Domain structure of PKC family members showing regulatory modules (pseudosubstrate sequence and C1, C2, and PB1 domains) and the kinase core. Shown below are the structures of the C1 domain of PKC 5 with bound phorbol (purple), the C2 domain of PKC (3 with bound Ca2+ (pink spheres), and the recently solved structure of the kinase domain by Grant and coworkers [1] of PKC pil with phosphorylation sites indicated in pink. Figure adapted from Newton (2003). 

S6K1 (also known as p70S6 kinase) is a serine/ threonine protein kinase which is involved in the regulation of translation by phosphorylating the 40S ribosomal protein S6. Insulin and several growth factors activate the kinase by phosphorylation in a PI 3-kinase dependent and rapamycin-sensitive manner. Phosphorylation of S6 protein leads to the translation of mRNA with a characteristic 5 polypyrimidine sequence motif. 

HSFl phosphorylation must be sensitive to nonheat inducers of HSF-DNA binding activity because HSFl phosphorylation can be achieved at 37 °C by other inducers of the HS response. HSF 1 contains polypeptide sequences that could serve as substrates for well characterized protein kinases, but few of these are known to be heat inducible. One family of protein kinases, the S6 protein kinases, have already been shown to exhibit heat inducible activity however, their peak level of activity during HS occurs well after the maximal induction of HSF phosphorylation (Jurivich et al., 1991). Thus, other protein kinases are likely to be directly linked to the phosphorylation of HSF. Some of the putative protein phosphorylation sites on HSF include motifs for protein kinase C, casein kinase, and enterokinase. There are tyrosine sequences that match substrates for known tyrosine kinases, but whether these residues are accessible to phosphorylation is not established. 

Fig. 4.1 Topological organization of the vanilloid receptor TRP VI. Highlighted are the molecular determinants of TRPVl regulation, such as recognition (binding) domains for capsaicin and acids, and phosphorylation sites for protein kinases. Numbers designate the key amino acid residues deduced from the rTRPVl primary sequence. Adapted from Ferrer-Montaniel, A. et al. (2004) Fur. J. Biochem. 271, 1820—1826.

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