Disease relevance of STK4

• Furthermore, overexpression of Mst1 induces morphological changes characteristic of apoptosis in human B lymphoma cells [1].
• We have analyzed the status of the p16/MST-1/CDKN2 gene in 63 brain tumors from Japanese patients [2].

High impact information on STK4

• Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion [3].
• RAPL regulated the localization and kinase activity of Mst1. 'Knockdown' of the gene encoding Mst1 demonstrated its requirement for the induction of both a polarized morphology and integrin LFA-1 clustering and adhesion triggered by chemokines and T cell receptor ligation [3].
• Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1 [4].
• Here we show that MST3, a mammalian Ste20-like protein kinase, is able to phosphorylate NDR protein kinase at Thr444/Thr442 [5].
• We have examined the role of caspase-mediated cleavage of the Ste20-like kinases, mammalian sterile 20-like 1 and 2 (Mst1/Mst2), in the mechanism of human eosinophil and neutrophil apoptosis [6].

Biological context of STK4

• These studies therefore implicate a role for caspase- and H(2)O(2)-mediated cleavage of the Mst1 and the subsequent release of the 36-kd catalytic fragment in the mechanism of eosinophil apoptosis [6].
• Moreover, MST1 polypeptides, bound via wild-type NORE1A to Ras(G12V) (where G12V stands for Gly12Val), exhibit higher Thr183 phosphorylation compared with MST1 bound to NORE1A alone [7].
• Mst1 may therefore represent an important target for caspases during cell death which serves to amplify the apoptotic response [1].
• Nore1 and RASSF1 Regulation of Cell Proliferation and of the MST1/2 Kinases [8].
• Our study demonstrates a previously unknown function for Mst1 of relaying the Rap1-RAPL signal to induce cell polarity and adhesion of lymphocytes [3].

Anatomical context of STK4

• Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis [6].
• Endogenous MST1 immunoprecipitated from KB cells is specifically associated with substoichiometric amounts of the growth inhibitory polypeptides RASSF1A and NORE1A (novel Ras effector 1A; a Ras-GTP-binding protein) [7].
• Immunoprecipitation and immunofluorescence analyses revealed that Mst1 was associated with RASSF1A in cultured mammalian cells, with both proteins colocalizing to microtubules throughout the cell cycle [9].
• Accordingly, we show that the mRNA and protein of the melanocyte-specific isoform of Mitf (Mitf-M) are present in several cultured CCS cell lines (Su-ccs-1, DTC1, Kao, MST-1, MST-2 and MST-3) [10].

Associations of STK4 with chemical compounds

• Autophosphorylation of Mst1 on a serine residue close to one of the caspase sites inhibited caspase-mediated cleavage in vitro [1].
• Mammalian Sterile20-like kinase 1 (Mst1) is a ubiquitously expressed serine/threonine kinase which represents a member of the rapidly expanding family of enzymes related to the yeast Sterile20 kinase [11].
• In conclusion, our study not only confirms that MST1, glutathione S-transferase p1-1, glycoprotein IX and soluble PPase belong to MAPK pathways, but also provides seven novel molecules for the further study of the pathways [12].
• Knockdown of MST1 expression by small interfering RNA diminished bortezomib-induced apoptosis or caspase-3 activation [13].

Regulatory relationships of STK4

• Moreover, the stimulatory effect of RASSF1A overexpression on Fas-induced apoptosis was inhibited by depletion of Mst1 [9].

Other interactions of STK4

• Finally, Mst1 appears to function upstream of the protein kinase MEKK1 in the SAPK pathway [1].
• Here we have identified the kinase Mst1 as a critical effector of RAPL [3].
• Hpo most closely resembles the pro-apoptotic mammalian sterile20 kinases 1 and 2 (Mst1 and 2), and Salvador (Sav) has a human orthologue hSav (also called hWW45) [14].

Analytical, diagnostic and therapeutic context of STK4

• Size exclusion chromatography indicates that Mst1 is associated with a high molecular weight complex in cells, suggesting that other proteins may also oligomerize with this kinase [15].
• The same subjects underwent a modified step test (MST1) by adding 1 kg sandbags every 3 min to backpacks worn by the subjects, to provide incremental load [16].

References