Serine/threonine-protein kinase 24 is an enzyme that in humans is encoded by the STK24 gene [5] [6] [7] located in the chromosome 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 the mitogen-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 (see PAK3) contain a C-terminal catalytic domain and an N-terminal regulatory domain that has a CDC42-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 in yeast. [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 in central 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. Using tandem affinity purification with mass spectrometry, they found that CCM3 is the main protein that binds to STK24 in HEK293 cells. [12]
STK24 operates on serine and threonine residues and, as a response to oxidative stress and caspase activity, develops cell death. [8]
STK24 is activated by autophosphorylation at Thr-190 and phosphorylation at this site is essential for its function. Phosphorylation by protein kinase A activates the isoform B of STK24. [8]
The mutagenesis of four residues in STK24 have been carried out. In position 18, the replacement of threonine (T) with alanine (A) causes the reduction of phosphorylation 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 of aspartic 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 brain hippocampus and cerebral cortex. [8]
STK24 has been shown to interact with PDCD10, [13] [14] [15] TRAF3IP3, [15] STRN3, [14] [15] MOBKL3, [14] [15] STRN, [14] [15] SLMAP, [14] [15] PPP2R1A, [14] [15] CTTNBP2NL, [15] FAM40A [14] [15] and STRN4. [14] [15]
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.
AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the AKT2 gene. It influences metabolite storage as part of the insulin signal transduction pathway.
Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.
Serine/threonine-protein kinase 4 is an enzyme that in humans is encoded by the STK4 gene.
Calcium/calmodulin-dependent protein kinase type II gamma chain is an enzyme that in humans is encoded by the CAMK2G gene.
5'-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene.
Polo-like kinase 3 (Drosophila), also known as PLK3, is an enzyme which in humans is encoded by the PLK3 gene.
Serine/threonine-protein kinase MARK1 is an enzyme that in humans is encoded by the MARK1 gene.
Serine/threonine-protein kinase 3 is an enzyme that in humans is encoded by the STK3 gene.
Serine/threonine-protein kinase 38 is an enzyme that in humans is encoded by the STK38 gene.
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.
Calcium/calmodulin-dependent protein kinase kinase 1 is an enzyme that in humans is encoded by the CAMKK1 gene.
STE20-like serine/threonine-protein kinase is an enzyme that in humans is encoded by the SLK gene.
Misshapen-like kinase 1 is an enzyme that in humans is encoded by the MINK1 gene.
52 kDa repressor of the inhibitor of the protein kinase is an enzyme that in humans is encoded by the PRKRIR gene.
Serine/threonine-protein kinase 38-like is an enzyme that in humans is encoded by the STK38L gene.
STE20/SPS1-related proline-alanine-rich protein kinase is an enzyme that in humans is encoded by the STK39 gene.
Calcium-binding protein 39 is a protein that in humans is encoded by the CAB39 gene.
Serine/threonine-protein kinase 10 is an enzyme that in humans is encoded by the STK10 gene.
Serine/threonine-protein kinase 25 is an enzyme that in humans is encoded by the STK25 gene.
