title: Factors that modulate the Pkn4 kinase cascade in Myxococcus xanthus.
abstract: Myxococcus xanthus, a gram-negative developmental bacterium, contains a large number of protein Ser/Thr kinases (PSTKs). Among these PSTKs, Pkn4 is shown to be 6-phosphofructokinase (PFK) kinase. PFK associates with the regulatory domain of Pkn4 (Pkn4RD) and is activated 2.7-fold upon phosphorylation at Thr-226 by Pkn4. The activation of PFK is required to consume glycogen accumulated during early development and is essential for efficient sporulation. Three new factors, MkapA, MkapB and MkapC have been identified that associate with Pkn4 by the yeast two-hybrid screen and each contains well-known protein-protein interaction domains. MkapB interacts with Pkn4 in a phosphorylation-dependent manner and remains associated with Pkn4 after its phosphorylation. Binding of MkapB to Pkn4 prevents the interaction of Pkn4 with PFK and consequently PFK phosphorylation and activation. A pfk-pkn4 deletion mutant accumulates glycogen at a rate two folds higher than the parent strain, DZF1, at the stationary phase and early development stage, it is unable to consume glycogen during development and produces only 3.4% of the DZF1 spore yield. In contrast, an mkapB deletion mutant exhibits a 24 h delay in fruiting body formation, accumulates less glycogen in the stationary phase and gives rise to 6.4% of the DZF1 spore yield. In addition to Pkn4, MkapA associates with other membrane-associated PSTKs, Pkn1, Pkn2, Pkn8 and Pkn9, while MkapB associates with Pkn8 and Pkn9, and MkapC with Pkn8. These results indicate that there are complex PSTK networks in M. xanthus sharing common modulating factors.
authors.affiliation: Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nariya
authors.forename: Sumiko
authors.initials: S
authors.lastname: Inouye
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D016941:Myxococcus xanthus / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D010732:Phosphofructokinase-1 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013171:Spores, Bacterial / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D006003:Glycogen; D010732:Phosphofructokinase-1; D017346:Protein Serine-Threonine Kinases