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Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is [S/T*]PX[K/R], where S/T* is the phosphorylated serine or threonine, P is proline, X is any amino acid, K is lysine, and R is arginine.
cGMP-dependent protein kinase or protein kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle relaxation, platelet function, sperm metabolism, cell division, and nucleic acid synthesis.
Mitogen Activated Protein (MAP) kinase kinase kinase is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. Subsequently, MAP kinase kinase activates MAP kinase. Several types of MAPKKK can exist but are mainly characterized by the MAP kinases they activate. MAPKKKs are stimulated by a large range of stimuli, primarily environmental and intracellular stressors. MAPKKK is responsible for various cell functions such as cell proliferation, cell differentiation, and apoptosis. The duration and intensity of signals determine which pathway ensues. Additionally, the use of protein scaffolds helps to place the MAPKKK in close proximity with its substrate to allow for a reaction. Lastly, because MAPKKK is involved in a series of several pathways, it has been used as a therapeutic target for cancer, amyloidosis, and neurodegenerative diseases. In humans, there are at least 19 genes which encode MAP kinase kinase kinases:
The transforming growth factor beta (TGFB) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, cell migration, apoptosis, cellular homeostasis and other cellular functions. The TGFB signaling pathways are conserved. In spite of the wide range of cellular processes that the TGFβ signaling pathway regulates, the process is relatively simple. TGFβ superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor. The type I receptor then phosphorylates receptor-regulated SMADs (R-SMADs) which can now bind the coSMAD SMAD4. R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression.
Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.
Bone morphogenetic protein receptor type-1B also known as CDw293 is a protein that in humans is encoded by the BMPR1B gene.
Serine/threonine-protein kinase receptor R3 is an enzyme that in humans is encoded by the ACVRL1 gene.
Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.
WNK , also known as WNK1, is an enzyme that is encoded by the WNK1 gene. WNK1 is serine-threonine protein kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regulation of cation-Cl− cotransporters (CCCs) such as the sodium chloride cotransporter (NCC), basolateral Na-K-Cl symporter (NKCC1), and potassium chloride cotransporter (KCC1) located within the kidney. CCCs mediate ion homeostasis and modulate blood pressure by transporting ions in and out of the cell. WNK1 mutations as a result have been implicated in blood pressure disorders/diseases; a prime example being familial hyperkalemic hypertension (FHHt).
Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the SGK3 gene.
Polo-like kinase 3 (Drosophila), also known as PLK3, is an enzyme which in humans is encoded by the PLK3 gene.
Serine-threonine kinase receptor-associated protein is an enzyme that in humans is encoded by the STRAP gene.
MAP kinase-interacting serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the MKNK2 gene.
Serine/threonine protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4 gene. Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.
Serine/threonine protein kinase MST4, also known as mammalian STE20-like protein kinase 4 (MST-4), is a protein that in humans is encoded by the MST4 gene.
Ankyrin repeat domain-containing protein 26 is a protein that in humans is encoded by the ANKRD26 gene. This protein has a function that is not currently understood.
The FXYD protein family is a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the amino acid sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator.
The Walker A and Walker B motifs are protein sequence motifs, known to have highly conserved three-dimensional structures. These were first reported in ATP-binding proteins by Walker and co-workers in 1982.
In molecular biology, BAG domains are protein domains found in proteins which are modulators of chaperone activity, they bind to HSP70/HSC70 proteins and promote substrate release. The proteins have anti-apoptotic activity and increase the anti-cell death function of BCL-2 induced by various stimuli. BAG-1 binds to the serine/threonine kinase Raf-1 or Hsc70/Hsp70 in a mutually exclusive interaction. BAG-1 promotes cell growth by binding to and stimulating Raf-1 activity. The binding of Hsp70 to BAG-1 diminishes Raf-1 signalling and inhibits subsequent events, such as DNA synthesis, as well as arrests the cell cycle. BAG-1 has been suggested to function as a molecular switch that encourages cells to proliferate in normal conditions but become quiescent under a stressful environment.
Serine/threonine-protein kinase RIO1 is an enzyme that in humans is encode by the RIOK1 gene.
References
- ↑ "Entrez Gene: PX domain containing serine/threonine kinase".
- 1 2 Mao H, Ferguson TS, Cibulsky SM, Holmqvist M, Ding C, Fei H, Levitan IB (August 2005). "MONaKA, a novel modulator of the plasma membrane Na,K-ATPase". J. Neurosci. 25 (35): 7934–43. doi: 10.1523/JNEUROSCI.0635-05.2005 . PMC 6725465 . PMID 16135750.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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