Identification of a Novel ERK 1/2-Interacting A-Kinase Anchoring Protein

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Title: Identification of a Novel ERK 1/2-Interacting A-Kinase Anchoring Protein
Author: Jivan, Arif
Abstract: Initially identified in Chlamydomonas , radial spoke protein 3 (RSP3 ) is one of at least twenty identified radial spoke structural components of motile cilia and is required for axonemal sliding and flagellar motility . The mammalian orthologs for this and other radial spoke proteins , however , remain to be identified and fully characterized . Mammalian RSP3 was found to interact with ERK2 through a yeast two -hybrid screen designed to identify interactors that have a higher affinity for the phosphorylated , active form of ERK2 . Confirming this finding , the human homolog long form , RSP3H , co -immunoprecipitates with ERK1 /2 in HEK293 cells . Human RSP3 , and its larger alternative start site gene product , radial spoke protein 3 homolog (RSP3H ) , are phosphorylated by ERK1 /2 on threonine 286 in vitro and in cells . RSP3 /RSP3H are also phosphorylated in vitro by cAMP -dependent protein kinase (PKA ) . Additionally , we showed that human RSP3H functions as an A -kinase anchoring protein (AKAP ) , and its ability to bind to the regulatory subunits of PKA , RII and RII , is regulated by ERK1 /2 activity and phosphorylation . Interestingly , expression analysis of mRNA suggests RSP3 /RSP3H are also present in cells that are thought to contain a single primary cilium but not motile cilia . Immunofluorescence staining of primary cilia -containing cells indicates that RSP3 /RSP3H localize to nuclear punctae , specifically promyelocytic leukemia (PML ) bodies , suggesting a non -cilia related role for RSP3 /RSP3H in these cells . Functionally , RSP3 /RSP3H may localize ERK1 /2 to a distinct site of action within the cell and serve as a point of convergence of cAMP -dependent and PKA -mediated influence upon ERK1 /2 downstream signaling or vice versa . These data are the first to establish a connection between ERK1 /2 and what was once ostensibly thought to only be a ciliary component as well as to identify a novel ERK1 /2 -interacting AKAP .
URI: http : / /hdl .handle .net /2152 .5 /318
Date: 2009-06-17

Citation

Identification of a Novel ERK 1/2-Interacting A-Kinase Anchoring Protein. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /318 .

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