Ribosome S6 protein kinase (ribosomal56kinase, RSK) is an important member of cell signaling pathway. In 1985, irEkson and Xiler discovered a 90-cut protein kinase in Xenopus eggs, which can phosphorylate the 405 ribosomal subunit 56 protein, thereby promoting the translation of certain mRNAs and regulating cell growth and proliferation. Plays an important role in the process. This protein kinase is named RSK or 9Ps0rk. It was later discovered that the protein is a downstream substrate of mitogen-activated protein kinase. So far, four RSK subtypes have been found, which are widely expressed in higher eukaryotic cells. With the gradual progress of research, people have discovered that RSK plays an important role in various life activities, including regulating gene transcription, participating in cell cycle regulation, promoting cell proliferation and differentiation, regulating cell survival and apoptosis, and participating in the formation of learning and memory, etc. RSKL is a pseudokinase similar to RSK, named after its similarity to the RSK family. Their function is not completely clear. There are two human members, RSKL1 (RPS6KC1) and RSKL2 (RPS6KL1).
Signaling pathway
RSKL can be activated by a variety of extracellular signaling molecules, such as growth factors, cytokines, skin hormones, and neurotransmitters. Receptors of growth factors and cytokines activate RSKL through the intracellular tyrosine kinase pathway, and then participate in the cell differentiation and proliferation process by stimulating growth-related protein synthesis and the Ras-ERK pathway. Many skin hormones and neurotransmitters pass intracellular signaling molecules, such as protein kinase C (poretinkinaseC, pKC), and (phosphoinositol-3-3iknase, PI3K), intracellular calcium or cAMP, etc., activate the Ras-ERK pathway. Studies have shown that 50% of ERKZ and RSK form a complex in Xenopus egg cells, and activation of this complex can affect its downstream substrates, such as Yifan s, ERa and 505, mediate the subsequent response of cells. RSK can not only respond to a variety of stimuli, but also the distribution of its substrates is wide and varied. As an intracellular signal transmission molecule, RSK in the cytoplasm can be activated directly by cytoplasmic substrates after being stimulated by growth factors, or translocated to the periphery of the cell near the membrane region to act on membrane-related proteins; there are also some RSK enters the nucleus and acts on transcription factors in the nucleus to regulate gene transcription. Studies have found that in addition to phosphorylation of proteins in the ribosome complex, RSK can also make glycogen synthase-3 (GSK-3), lL cell adhesion molecules, RasGTIPGDP exchange factor, 505 and p34edeZ-inhibitory kinase Mytl are phosphorylated. In addition, the substrates of RSK also include transcription factor cAMP response element binding protein (CREB) and estrogen receptor. (ERa), IKB. N/F girl and e-Fos and other nuclear eggs White. At the same time, RSK can also be combined with molecular chaperones (such as CREB-binding protein and 3P00) to regulate certain cell life activities. It can be seen that RSK plays a very important role in the regulation of various cell functions.
Domain structure
RSKL has a PX domain, followed by a MIT domain, and then a kinase domain. There is no pkinase_C domain and no space at the C-terminus. Human RSKL2 is truncated at the N-terminus and lacks the PX domain. The MIT domain may interact with microtubules and be present in proteins involved in vacuolar classification and intracellular transport. The PX domain binds phosphoinositide and target proteins to the cell membrane. Sorted neurotoxin snx-15 is the only other human protein with PX and MIT domains. The RSKL kinase domain is a catalytic inactivated pseudokinase, lacking the DFG motif and catalytic loop.
Evolution
RSKL was found in all post-animals.
Functions
Human RSKL1 interacts with peroxidase 3 through its pseudokinase domain. It also binds to sphingosine kinase-1 and colocalizes with it in early endosomes. Endosomal positioning requires a PX domain. Both human RSKL proteins are reported to bind HSP90.
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