Lim Kinases
Encyclopedia
LIM kinase-1 and LIM kinase-2 (LIMK2
) are actin
-binding kinase
s that phosphorylate members of the ADF/cofilin
family of actin binding and filament severing protein
s. ADF/cofilin are the only substrate
s yet identified for the LIM kinases. Upstream, LIMK1 is regulated by Pak1, and LIMK2 by the Rho-dependent kinase ROCK. Lim Kinases are activated by PAK (p21-activated kinase).
There are approximately 40 known eukaryotic LIM protein
s, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc
fingers. Although zinc fingers usually function by binding to DNA
or RNA
, the LIM motif
probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase
domain. LIMK1 is likely to be a component of an intracellular signaling pathway and may be involved in brain development. LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome
.
LIMK2
LIM domain kinase 2 is an enzyme that in humans is encoded by the LIMK2 gene.-External links:* Info with links in the...
) are actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
-binding kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
s that phosphorylate members of the ADF/cofilin
Cofilin
ADF/cofilin is a family of actin-binding proteins which disassembles actin filaments.Three highly conserved and highly identical genes belonging to this family have been described in human and mice:...
family of actin binding and filament severing protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. ADF/cofilin are the only substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
s yet identified for the LIM kinases. Upstream, LIMK1 is regulated by Pak1, and LIMK2 by the Rho-dependent kinase ROCK. Lim Kinases are activated by PAK (p21-activated kinase).
There are approximately 40 known eukaryotic LIM protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
fingers. Although zinc fingers usually function by binding to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
or RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
, the LIM motif
Structural motif
In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a supersecondary structure, which appears also in a variety of other molecules...
probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
domain. LIMK1 is likely to be a component of an intracellular signaling pathway and may be involved in brain development. LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome
Williams syndrome
Williams syndrome is a rare neurodevelopmental disorder characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers; developmental delay coupled with strong language skills; and cardiovascular problems, such as...
.