SPAK, a STE20/SPS1-related kinase that activates the p38 pathway.
We have cloned a member of the STE20/SPS1 protein kinase family from a transformed rat pancreatic beta cell line. SPAK (STE20/SPS1-related, proline alanine-rich kinase) belongs to the SPS1 subfamily of STE20 kinases and is highly conserved between species. SPAK is expressed ubiquitously, although preferentially in brain and pancreas. Biochemical characterization of SPAK catalytic activity demonstrates that is a serine/threonine kinase that can phosphorylate itself and an exogenous substrate in vitro. SPAK is immunoprecipitated from transfected mammalian cells as a complex with another, as yet uncharacterized, serine/threonine kinase which is capable of phosphorylating catalytically-inactive SPAK and myelin basic protein in an in vitro kinase assay. SPAK specifically activates the p38 pathway in cotransfection assays. Like MST1 and MST2, SPAK contains a putative caspase cleavage site at the junction of the catalytic domain and the C-terminal region. Full-length SPAK is expressed in the cytoplasm in transfected cells, while a mutant corresponding to caspase-cleaved SPAK is expressed predominantly in the nucleus. The similarity of SPAK to other SPS1 family members, its ability to activate the p38 pathway, in addition to its putative caspase cleavage site, provide evidence that SPAK may act as a novel mediator of stress-activated signals. Oncogene (2000) 19, 4290 - 4297
Johnston
A M
AM
Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Parkville 3050, Australia.
Naselli
G
G
Gonez
L J
LJ
Martin
R M
RM
Harrison
L C
LC
DeAizpurua
H J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D018076:DNA, Complementary / Q000235:genetics; D004790:Enzyme Induction; D005796:Genes; D006801:Humans; D007515:Islets of Langerhans / Q000201:enzymology / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D009928:Organ Specificity; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013312:Stress, Physiological / Q000201:enzymology; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases