Radial spoke protein 3 is a mammalian protein kinase A-anchoring protein that binds ERK1/2.
Initially identified in Chlamydomonas, RSP3 (radial spoke protein 3) is 1 of more than 20 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 characterized. We found mammalian RSP3 to bind to the MAPK ERK2 through a yeast two-hybrid screen designed to identify interacting proteins that have a higher affinity for the phosphorylated, active form of the protein kinase. Consistent with the screening result, the human homolog, RSPH3, interacts with and is a substrate for ERK1/2. Moreover, RSPH3 is a protein kinase A-anchoring protein (AKAP) that scaffolds the cAMP-dependent protein kinase holoenzyme. The binding of RSPH3 to the regulatory subunits of cAMP-dependent protein kinase, RIIalpha and RIIbeta, is regulated by ERK1/2 activity and phosphorylation. Here we describe an ERK1/2-interacting AKAP and suggest a mechanism by which cAMP-dependent protein kinase-AKAP binding can be modulated by the activity of other enzymes.
Jivan
Arif
A
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Earnest
Svetlana
S
Juang
Yu-Chi
YC
Cobb
Melanie H
MH
D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques
D054758:A Kinase Anchor Proteins; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D009419:Nerve Tissue Proteins; C517819:PRKAR2A protein, human; C544862:RSPH3 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
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