Serine/threonine-protein kinase 24 is anenzyme that in humans is encoded by theSTK24gene[5][6][7] located in thechromosome 13, band q32.2. It is also known as Mammalian STE20-like protein kinase 3 (MST-3).[8] The protein is 443 amino acids long and its mass is 49 kDa.[8]
The yeast 'Sterile 20' gene (STE20) functions upstream of themitogen-activated protein kinase (MAPK) cascade. In mammals, protein kinases related to STE20 can be divided into 2 subfamilies based on their structure and regulation. Members of the PAK subfamily (seePAK3) contain aC-terminal catalytic domain and anN-terminal regulatory domain that has aCDC42-binding domain. In contrast, members of the GCK subfamily (MAP4K2), also called the Sps1 subfamily, have an N-terminal catalytic domain and a C-terminal regulatory domain without a CDC42-binding domain. STK24 belongs to the GCK subfamily of STE20-like kinases.[6][7]
The sterile 20 protein was first found inyeast.[9] The MST-20 related kinases family is growing, having 28 members divided into two groups - p21-activated kinase and germinal center kinase (GCK) families.[10] STK24 belongs to the germinal center kinase (GCK) III subfamily of sterile 20 kinases.
Kinases of GCKIII subfamily are involved in regulation of multiple functions of the cells[10] and interaction with programmed cell death 10 (CCM3).[11] CCM is a pathological vascular situation that, influencing the blood vessels incentral nervous system (CNS), may cause stroke, seizure and even cerebral hemorrhage.[12] It has been shown that STK24 and STK25 operate in the same cardiovascular development pathway with CCM3. According to the results of the experiment by Zhang et al.,[12] lack of STK24 has no effect on the amount of neutrophils or leucocytes, as well as it does not affect the chemotaxis of neutrophils.[12] Zhang et al. also the interaction between STK24 and CCM. Usingtandem affinity purification withmass spectrometry, they found that CCM3 is the main protein that binds to STK24 in HEK293 cells.[12]
STK24 operates onserine andthreonine residues and, as a response to oxidative stress and caspase activity, develops cell death.[8]
STK24 is activated byautophosphorylation at Thr-190 and phosphorylation at this site is essential for its function. Phosphorylation byprotein kinase A activates the isoform B of STK24.[8]
Themutagenesis of four residues in STK24 have been carried out. In position 18, the replacement ofthreonine (T) withalanine (A) causes the reduction ofphosphorylation by PKA.[6] the modification in positions 65, where lysine (K) is replaced with A, and the position 190, where T is replaced with A, affects the activity and autophosphorylation.[10] In residue 321, the change ofaspartic acid (D) to Asparagine (N) reveals as loss of proteolytic cleavage by caspases.[10] Those residues may play an important role apoptotic signal transduction.[10]
STK24 has two subunits, 36kDa N-terminal subunit and 12 kDa C-terminal subunit.[8] In the cells, STK24 is located in nucleus and less in cytoplasm and membrane. There are two isoforms of the protein, isoform A is ubiquitous and is expressed in 237 organs, isoform B is expressed in brainhippocampus andcerebral cortex.[8]
Christian SL, McDonough J, Liu Cy CY, Shaikh S, Vlamakis V, Badner JA, Chakravarti A, Gershon ES (May 2002). "An evaluation of the assembly of an approximately 15-Mb region on human chromosome 13q32-q33 linked to bipolar disorder and schizophrenia".Genomics.79 (5):635–56.doi:10.1006/geno.2002.6765.PMID11991713.
