Kinase Domain Cell Biology
The structure of janus kinases jaks is unique among protein tyrosine kinases in having tandem nonidentical kinase and pseudokinase domains.
Kinase domain cell biology. Two of these domains the n terminal ferm domain and the kinase domain form an auto inhibitory interaction. Sh2 domains allow proteins containing those domains to dock to phosphorylated tyrosine residues on other proteins. The pseudokinase interface surface is primarily composed of residues in the αc helix β4 loop the extended β7 β8 loop and the n terminal.
Sh2 domains are commonly found in adaptor proteins that aid in the signal transduction of receptor tyrosine kinase pathways. Lack of jak3 expression results in severe combined immunodeficiency scid. Protein kinase cθ pkcθ is a serine threonine kinase that plays an essential role in antigen regulated responses of t lymphocytes.
These experiments demonstrated a connection between p185 dimerization and cellular transformation. Despite its conservation in evolution however the function of the pseudokinase domain remains poorly understood. The pseudosubstrate domain dark blue precedes the c1 domain in protein kinase c.
Focal adhesion kinase has four defined regions or tertiary structure domains. This interaction thought to be the result of hydrophobic interactions between the two domains 20 prevents the activation of the kinase domain thereby preventing the signalling function of fak. 88 89 it consists of a protein kinase domain a calcium calmodulin binding region an ankyrin repeat domain two putative p loops a cytoskeletal binding region and a death domain.
The interaction between the tyk2 pseudokinase and kinase domains is predominantly mediated by the n lobes of each domain with the back of the pseudokinase n lobe interacting at a near 90 angle with the underside of the kinase domain n lobe β1 β3 sheet and the β2 β3 loop as well as the hinge region and subsequent αd helix fig. The c2 domain turquoise has been implicated in ca 2 dependent binding to acidic lipids and is also present in synaptotagmin and phospholipase a2 among others the purple box in synaptotagmin represents its transmembrane domain. Cell lines transfected with this mutant protein were not transformed demonstrating that a functional kinase is necessary for the transforming potency of p185 neu.
90 emerging evidence suggests that elevated dapk1 activity is linked to neuronal injury such as ischemic injury and seizure related injury. Protein kinase c pkc enzymes comprise a family of serine threonine kinases that regulate a broad array of cellular processes spitaler and cantrell 2004 although t lymphocytes express multiple pkc enzymes considerable evidence indicates that pkcθ is the most important isoform for transmission of activating signals from the t cell receptor tcr to nuclear targets. Death associated protein kinase dapk1 is a serine threonine protein kinase that participates in apoptotic cell death growth factor signaling and autophagy.