title: Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3.
abstract: Phospholipase C (PLC)-beta enzymes (isoenzymes beta 1-beta 4) are activated by G protein subunits, leading to the generation of intracellular messengers which mobilize calcium and activate protein kinase C. It has recently been recognized that these enzymes interact with and are regulated by proteins other than G proteins. Using the yeast two-hybrid technique to screen a leukocyte library we identified mitogen-activated protein kinase kinase 3 (MKK3) as a partner of PLC-beta 2. The interaction was confirmed by co-immunoprecipitation assays which indicated that MKK3 interacts with PLC-beta 2, but not with other PLC-betas. PLC-beta 2 interacted weakly with MKK6, which is related to MKK3, but not with the other MKK3 tested. The region of PLC-beta 2 involved in the interaction with MKK3 was mapped to the C-terminus of PLC-beta 2. p38MAPK also co-immunoprecipitated with PLC-beta 2. The data suggest that PLC-beta 2 serves an unappreciated role assembling components of the p38MAPK signaling module.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. bar0003@mc.duke.edu
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Barr
authors.forename: Robin
authors.initials: R
authors.lastname: Marjoram
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Ralph
authors.initials: R
authors.lastname: Snyderman
mesh_terms: D003001:Cloning, Molecular; D015723:Gene Library; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007962:Leukocytes / Q000201:enzymology*; D048371:MAP Kinase Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D054799:Phospholipase C beta; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D010738:Type C Phospholipases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D007527:Isoenzymes; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; C482530:MAP2K3 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D010738:Type C Phospholipases; C518033:PLCB1 protein, human; D054799:Phospholipase C beta