drosophila heat shock response requires the jnk pathway and phosphorylation of mixed lineage kinase at a conserved serine-proline motif果蝇热休克反应需要物通路和混合血统的磷酸化激酶守恒serine-proline图案.pdfVIP

Drosophila Heat Shock Response Requires the JNK Pathway and Phosphorylation of Mixed Lineage Kinase at a Conserved Serine-Proline Motif 1 2 2 Rebecca L. Gonda , Rebecca A. Garlena , Beth Stronach * 1 Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 2 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America Abstract Defining context specific requirements for proteins and pathways is a major challenge in the study of signal transduction. For example, the stress-activated protein kinase (SAPK) pathways are comprised of families of closely related transducers that are activated in a variety of tissues and contexts during development and organismal homeostasis. Consequently, redundant and pleiotropic effects have hampered a complete understanding of the individual contributions of transducers in distinct contexts. Here, we report on the function of a context-specific regulatory phosphorylation site, PXSP, in the Drosophila mixed lineage kinase protein, Slpr, a mitogen-activated protein kinase kinase kinase (MAP3K) in the Jun Kinase (JNK) pathway. Genetic analysis of the function of non-phosphorylatable (PXAP) and phosphomimetic mutant (PXEP) Slpr transgenes in several distinct contexts revealed minimal effects in JNK-dependent tissue closure processes but differential requirements in heat stress response. In particular, PXAP expression resulted in sensitivity of adults to sustained heat shock, like p38 and JNK pathway mutants. In contrast, PXEP overexpression conferred some resistance. Indeed, phosphorylation of the PXSP motif is enriched under heat shock conditions and requires in part, the p38 kinases for the enrichment. T