Pseudokinases, Tribbles Proteins and Cancer
نویسندگان
چکیده
The human kinome comprises 518 protein kinases, of which approximately 10% lack one or more the conserved amino acids necessary for catalytic activity [...]
منابع مشابه
Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease
The Tribbles (TRIB) pseudokinases control multiple aspects of eukaryotic cell biology and evolved unique features distinguishing them from all other protein kinases. The atypical pseudokinase domain retains a regulated binding platform for substrates, which are ubiquitinated by context-specific E3 ligases. This plastic configuration has also been exploited as a scaffold to support the modulatio...
متن کاملRethinking Pseudokinases
Pseudokinases lack conservation of one or more of the catalytic residues in the kinase core and as a consequence are typically thought to be catalytically inactive. New work by Mukherjee et al. (2008) challenges this assumption. They show that the pseudokinase domain of CASK (Ca2+/calmodulin activated serine-threonine kinase) adopts an active conformation and displays catalytic activity in vivo.
متن کاملEmerging roles of pseudokinases.
Kinases control virtually all aspects of biology. Forty-eight human proteins have a kinase-like domain that lacks at least one of the conserved catalytic residues; these proteins are therefore predicted to be inactive and have been termed pseudokinases. Here, we describe exciting work suggesting that pseudokinases, despite lacking the ability to phosphorylate substrates, are still pivotal in re...
متن کاملPseudokinases from a structural perspective.
The catalytic (C) subunit of PKA was the first protein kinase structure to be solved, and it continues to serve as the prototype for the protein kinase superfamily. In contrast, by comparing many active and inactive kinases, we developed a novel 'spine' concept where every active kinase is composed of two hydrophobic spines anchored to a hydrophobic F-helix. The R-spine (regulatory spine) is dy...
متن کاملNucleotide-binding mechanisms in pseudokinases
Pseudokinases are classified by the lack of one or several of the highly conserved motifs involved in nucleotide (nt) binding or catalytic activity of protein kinases (PKs). Pseudokinases represent ∼10% of the human kinome and they are found in all evolutionary classes of kinases. It has become evident that pseudokinases, which were initially considered somewhat peculiar dead kinases, are impor...
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ژورنال
عنوان ژورنال: Cancers
سال: 2023
ISSN: ['2072-6694']
DOI: https://doi.org/10.3390/cancers15143547