Protein kinases transfer a phosphate group from ATP to a serine, threonine or tyrosine residue on a protein peptide substrate, directly affecting the activity and function of the target. Radiolabeling studies have shown that about 30% of proteins in eukaryotic cells are phosphorylated. Kinase activity is a key post-translational modification that regulates a wide range of cellular activities, including cell cycle, differentiation, metabolism, and neuronal communication. In addition, the aberrant activities of Akt, ERK, JNK, PKC, PKA, p38 and other MAPKs are associated with many disease states.
The serine-threonine protein kinase AKT1 is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and related AKT2 are activated by platelet-derived growth factors. Activation is rapid and specific, and it is abolished by mutations in the pleckstrin homology domain of AKT1. Activation by phosphatidylinositol 3-kinase is shown. In the developing nervous system, AKT is a key mediator of growth factor-induced neuronal survival. Survival factors can inhibit apoptosis by activating the serine/threonine kinase AKT1 in a transcription-independent manner, and then activating phosphorylation and inactivation of the components of the apoptotic machinery. Mice lacking AKT1 lost 25% of their body weight, suggesting thatAKT1 is critical for the transmission of growth-promoting signals, most likely through the IGF1 receptor. Mice lacking AKT1 are also resistant to cancer: they experience considerable delay in tumor growth triggered by large T antigens or Neu oncogenes. A single nucleotide polymorphism in this gene causes Proteus syndrome.
AKT (now also known as AKT1) was originally identified as an oncogene in transformed retroviruses, and AKT8.AKT8 was isolated from a spontaneous thymoma cell line derived from AKR mice by co-culture with an indicator sputum cell line. The transformed cell sequence v-akt was cloned from the transformed sputum cell clone and used to identify AKT1 and AKT2 in the human clone library. AKT8 was isolated by Stephen Staal in the laboratory of Wallace P. Rowe; he then cloned v-akt and human AKT1 and AKT2 at the Johns Hopkins University Cancer Center staff. In 2011, AKT1 mutations were closely related to amoeba syndrome, which may affect elephants. The name Akt represents the transformation of the Ak strain. The origin of the Akt name dates back to 1928, in which J. Furth conducted an experimental study of mice with spontaneous thymic lymphoma. Mice from three different populations were studied and the populations were designated as A, R and S. It was noted that population A produced many cancers, followed by a second inferior letter (Aa, Ab, Ac, etc.) to specify the inbred family. Therefore, it comes from the Ak strain mouse. In 1936, Ak mice were further inbred at the Rockefeller Institute, leading to the naming of the AKR mouse strain. In 1977, transformed retroviruses were isolated from AKR mice. The virus was named Akt-8 and "t" represents its ability to transform.
MAPKs is an important transmitter of signals from the cell surface to the interior of the nucleus. Mitogen-activated protein kinase (MAPKs) is a group of serine-threonine that can be activated by different extracellular stimuli such as cytokines, neurotransmitters, hormones, cellular stress and cell adhesion. Protein kinase. MAPK is named because it is activated when cells are activated by stimulation with mitogens such as growth factors. All eukaryotic cells express MAPKs. The basic composition of the MAPKs pathway is a three-stage kinase pattern that is conserved from yeast to humans, including MAPKs kinase kinase (MKKK), MAPKs kinase (MKK), and MAPKs. It is activated in turn to regulate various important cell physiology/pathological processes such as cell growth, differentiation, stress adaptation to the environment, and inflammatory response. Mitogen-activated protein kinases (MAP kinases, MAPKs) chains are one of the important pathways in eukaryotic signaling networks and play a key role in gene expression regulation and cytoplasmic function. The MAPKs chain consists of three classes of protein kinases, MAP3K-MAP2K-MAPK, which transmit upstream signals to downstream response molecules by sequential phosphorylation.
Protein kinase A (PKA) is a type of cyclic AMP-dependent enzyme, also known as cAMP-dependent protein kinase A (cyclic-AMP). The role of PKA in cells is to regulate glycogen, metabolic lipids and so on. Protein kinase A (PKA) was first discovered by chemists H. Fischer and Edwin G. Krebs in 1968. They won the 1992 Nobel Prize in Physiology or Medicine for their work on phosphorylation and dephosphorylation and PKA activity. PKA is one of the most popular protein kinases which have been studied, in part because of its uniqueness. Among the 540 different protein kinase genes in humans, except for PKA, only casein kinase 2 is known to exist as a tetramer. After Stan Knight et al. discovered that PKA might have four C subunits and four R subunits, people began to realize the diversity of mammalian PKA subunits. In 1991, Susan Taylor and others obtained the internal structure of the subunit for the first time through the crystallization method, providing a model for the study of other kinases.
Protein kinase C (PKC) is a family of serine and threonine-specific protein kinases that are activated by calcium and second messenger diacylglycerols (Figure 1). Members of the PKC family phosphorylate a variety of protein targets and are known to be involved in a variety of cellular signaling pathways. Members of the PKC family are also the main receptors for phorbol esters, and phorbol esters are a class of tumor promoters. Each member of the PKC family has a specific expression profile and is thought to play a unique role in the cell. The protein encoded by this gene is one of the members of the PKC family. The kinase has been reported to play a role in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoints, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of myocardial contractility and intracellular Ca2+ treatment.
1. Remy I.; et al. Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt. Molecular and Cellular Biology, 2004, 24 (4): 1493-504.
2. Guan KL.; et al. Negative regulation of the serine/threonine kinase B-Raf by Akt. The Journal of Biological Chemistry. 2000, 275 (35): 27354-27359.