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CGMP-dependent protein kinase

 

 
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CGMP-dependent protein kinase
 
 
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cGMP-dependent protein kinase or Protein Kinase G (PKG) is a serine/threonine-specific protein kinase
Serine/threonine-specific protein kinase

Serine/threonine protein kinases phosphorylate the OH group of serine or threonine .At least 125 of the 500+ human protein kinases are serine/threonine kinases ....
 that is activated by cGMP
Cyclic guanosine monophosphate

Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP, most notably by activating intracellular protein kinases in response to the binding of cell membrane-impermeable peptide hormones to the external cell surface....
. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle
Smooth muscle

Smooth muscle is a type of non-striated muscle, found within the tunica media layer of large and small arteries and veins, the urinary bladder, uterus, male and female reproductive tracts, gastrointestinal tract, respiratory tract, the ciliary muscle, and iris of the eye....
 relaxation, platelet
Platelet

Platelets, or Thrombocyte, are small, irregularly shaped anuclear cells, 2-4?m in diameter, which are derived from fragmentation of precursor megakaryocytes....
 function, sperm
Spermatozoon

A sperm, from the ancient Greek word sp???a and and more commonly known as a sperm cell, is the ploidy cell that is the male gamete. It Fertilization an ovum to form a zygote....
 metabolism, cell division
Cell division

Cell division is a process by which a cell , called the parent cell, divides into two or more cells, called daughter cells. Cell division is usually a small segment of a larger cell cycle....
 ,and nucleic acid
Nucleic acid

A nucleic acid is a macromolecule composed of chains of monomeric nucleotides. In biochemistry these molecules carry genetic information or form structures within Cell ....
 synthesis.

are serine/threonine kinases that are present in a variety of eukaryote
Eukaryote

Animals, plants, fungus, and protists are eukaryotes , organisms whose Cell are organized into complex structures enclosed within Cell membrane....
s ranging from the unicellular organism Paramecium
Paramecium

Paramecia, also known as Lady Slippers, due to their appearance, are a group of unicellular ciliate protozoa, which are commonly studied as a representative of the ciliate group, and range from about 50 to 350 micrometre in length, Simple cilia cover the body, which allow the cell to move with a synchronous motion ....
 to humans.






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cGMP-dependent protein kinase or Protein Kinase G (PKG) is a serine/threonine-specific protein kinase
Serine/threonine-specific protein kinase

Serine/threonine protein kinases phosphorylate the OH group of serine or threonine .At least 125 of the 500+ human protein kinases are serine/threonine kinases ....
 that is activated by cGMP
Cyclic guanosine monophosphate

Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP, most notably by activating intracellular protein kinases in response to the binding of cell membrane-impermeable peptide hormones to the external cell surface....
. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle
Smooth muscle

Smooth muscle is a type of non-striated muscle, found within the tunica media layer of large and small arteries and veins, the urinary bladder, uterus, male and female reproductive tracts, gastrointestinal tract, respiratory tract, the ciliary muscle, and iris of the eye....
 relaxation, platelet
Platelet

Platelets, or Thrombocyte, are small, irregularly shaped anuclear cells, 2-4?m in diameter, which are derived from fragmentation of precursor megakaryocytes....
 function, sperm
Spermatozoon

A sperm, from the ancient Greek word sp???a and and more commonly known as a sperm cell, is the ploidy cell that is the male gamete. It Fertilization an ovum to form a zygote....
 metabolism, cell division
Cell division

Cell division is a process by which a cell , called the parent cell, divides into two or more cells, called daughter cells. Cell division is usually a small segment of a larger cell cycle....
 ,and nucleic acid
Nucleic acid

A nucleic acid is a macromolecule composed of chains of monomeric nucleotides. In biochemistry these molecules carry genetic information or form structures within Cell ....
 synthesis.

Genes and proteins

PKG are serine/threonine kinases that are present in a variety of eukaryote
Eukaryote

Animals, plants, fungus, and protists are eukaryotes , organisms whose Cell are organized into complex structures enclosed within Cell membrane....
s ranging from the unicellular organism Paramecium
Paramecium

Paramecia, also known as Lady Slippers, due to their appearance, are a group of unicellular ciliate protozoa, which are commonly studied as a representative of the ciliate group, and range from about 50 to 350 micrometre in length, Simple cilia cover the body, which allow the cell to move with a synchronous motion ....
 to humans. Two PKG gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
s, coding for PKG type I (PKG-I) and type II (PKG-II), have been identified in mammal
Mammal

Mammals are a class of vertebrate animals whose name is derived from their distinctive feature, mammary glands, with which they feed their young....
s. The N-terminus of PKG-I is encoded by two alternatively spliced exon
Exon

An exon in a gene is a DNA or RNA sequence that is translated into RNA or protein. In contrast, an intron is a DNA sequence in the gene that is not translated....
s that specify for the PKG-Ia and PKG-Iß isoforms. PKG-Iß is activated at ~10-fold higher cGMP concentrations than PKG-Ia. The PKG-I and PKG-II are homodimers of two identical subunits
Protein subunit

In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein....
 (~75 kDa and ~85 kDa, respectively) and share common structural features.

Each subunit is composed of three functional domains:

  • (1) an N-terminal domain that mediates homodimerization, suppression of the kinase activity in the absence of cGMP, and interactions with other proteins including protein substrates
  • (2) a regulatory domain that contains two non-identical cGMP-binding sites
  • (3) a kinase domain that catalyzes the phosphate
    Phosphate

    A phosphate, an inorganic chemical, is a Salt of phosphoric acid. Inorganic phosphates are mining to obtain phosphorus for use in agriculture and industry....
     transfer from ATP
    Adenosine triphosphate

    This article is about the chemical used by cells as an energy carrier. For other uses, see ATP .Adenosine-5'-triphosphate is a multifunctional nucleotide, and plays an important role in cell biology as a coenzyme that is the "molecule unit of currency" of intracellular energy transfer....
     to the hydroxyl
    Hydroxyl

    Hydroxyl in chemistry stands for a molecule consisting of an oxygen atom and a hydrogen atom connected by a covalent bond. The neutral form is a hydroxyl Radical and the hydroxyl anion is called a hydroxide....
     group of a serine/threonine side chain
    Side chain

    A side chain in organic chemistry and biochemistry is a part of a molecule that is attached to a core structure. The placeholder R is often used as a generic placeholder for side chains, the R historically being derived from radical or rest....
     of the target protein


Binding of cGMP to the regulatory domain induces a conformational change that releases the inhibition of the catalytic core by the N-terminus and allows the phosphorylation
Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Protein phosphorylation in particular plays a significant role in a wide range of cellular processes....
 of substrate proteins. Whereas PKG-I is predominantly localized in the cytoplasm
Cytoplasm

The cytoplasm is the part of a Cell that is enclosed within the plasma membrane. In eukaryote cells the cytoplasm contains organelles, such as mitochondrion, that are filled with liquid kept separate from the rest of the cytoplasm by biological membranes....
, PKG-II is anchored to the plasma membrane by N-terminal myristoylation
Myristoylation

Myristoylation is an irreversible, co-translational protein modification found in animals, plants, fungi and viruses. In this protein modification a myristoyl group is covalently attached via an amide bond to the alpha-amino group of an N-terminal amino acid of a nascent polypeptide....
.

Tissue distribution

In general, PKG-I and PKG-II are expressed in different cell types.
  • PKG-I has been detected at high concentrations (above 0.1 µmol/L) in all types of smooth muscle cells (SMCs) including vascular
    Blood vessel

    The blood vessels are the part of the circulatory system that transport blood throughout the body. There are three major types of blood vessels: the artery, which carry the blood away from the heart, the capillary, which enable the actual exchange of water and chemicals between the blood and the tissues; and the veins, which carry blood from...
     SMCs and in platelet
    Platelet

    Platelets, or Thrombocyte, are small, irregularly shaped anuclear cells, 2-4?m in diameter, which are derived from fragmentation of precursor megakaryocytes....
    s. Lower levels are present in vascular endothelium
    Endothelium

    The endothelium is the thin layer of cell that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall....
     and cardiomyocytes. The enzyme is also expressed in fibroblast
    Fibroblast

    A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen , the structural framework for animal tissues, and play a critical role in wound healing....
    s, certain types of renal cells and leukocytes, and in specific regions of the nervous system
    Nervous system

    The nervous system is a Neural network of specialized cells that communicate information about an animal's surroundings and itself. It processes this information and causes reactions in other parts of the body....
    , for example in the hippocampus
    Hippocampus

    The hippocampus is a brain structure located inside the medial temporal lobe of the cerebral cortex, and therefore is part of the telencephalon ....
    , in cerebellar
    Cerebellum

    The cerebellum is a region of the brain that plays an important role in the integration of perception, coordination and motoneuron control. In order to coordinate motor control, there are many neural pathways linking the cerebellum with the cerebrum motor cortex and the spinocerebellar tract ....
     Purkinje cells, and in dorsal root ganglia. Neuron
    Neuron

    Neurons are responsive cell in the nervous system that process and transmit information by electrochemical Signal . They are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves....
    s express either the PKG-Ia or the PKG-Iß isoform, platelets predominantly Iß, and both isoforms are present in smooth muscle.
  • PKG-II has been detected in renal cells, zona glomerulosa
    Zona glomerulosa

    The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule....
     cells of the adrenal cortex
    Adrenal cortex

    Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively....
    , Clara cell
    Clara cell

    Clara cells are non-mucous and non-ciliated secretion cell found in the primary bronchioles of the lungs.Clara cells are dome-shaped and have short microvilli....
    s in distal airway
    Airway

    The airways are those parts of the respiratory system through which air flows, to get from the external environment to the alveoli.The airway begins at the mouth or nose, and accesses the vertebrate trachea via the pharynx....
    s, intestinal mucosa
    Intestine

    In anatomy, the intestine is the segment of the Gastrointestinal tract extending from the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine....
    , pancreatic ducts
    Pancreas

    The pancreas is a gland Organ in the digestive system and endocrine system of vertebrates. It is both an endocrine gland , as well as an exocrine gland, secreting pancreatic juice containing Digestion enzymes that pass to the small intestine....
    , parotid and submandibular gland
    Submandibular gland

    The paired submandibular glands are salivary glands located beneath the floor of the mouth. In humans, they account for 70% of the salivary volume and weigh about 15 grams....
    s, chondrocyte
    Chondrocyte

    Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans....
    s, and several brain cell nuclei
    Cell nucleus

    In cell biology, the nucleus , also sometimes referred to as the "control center", is a membrane-enclosed organelle found in all eukaryote cell ....
    , but not in cardiac and vascular myocyte
    Myocyte

    A myocyte is the type of Cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long chains of sarcomeres, the contractile units of the cell....
    s.


Specifically, in smooth muscle tissue, PKG phosphorylates the Myosin light chain phosphatase which dephosphorylates the myosin light chains initiating smooth muscle relaxation.

Role in Cancer

On 18 July 2007 it was discovered that cancerous colon cells stop producing PKG, which apparently limits beta-catenin
Beta-catenin

Beta-catenin is a subunit of the cadherin protein complex. In Drosophila, the homologous protein is called armadillo. Beta-catenin has been implicated as an integral component in the Wnt signaling pathway....
 thus allowing the VEGF enzyme to solicit angiogenesis.

See also

  • cAMP-dependent protein kinase
    CAMP-dependent protein kinase

    In cell biology, protein kinase A refers to a family of enzymes whose activity is dependent on the level of cyclic AMP in the cell. PKA is also known as cAMP-dependent protein kinase )....


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