The Balpha and Bdelta regulatory subunits of PP2A are necessary for assembly of the CaMKIV.PP2A signaling complex.
Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a serine/threonine kinase that is important in synaptic plasticity and T cell maturation. Activation of CaMKIV requires calcium/calmodulin binding and phosphorylation at T200 by CaMK kinase. Our previous work has shown that protein serine/threonine phosphatase 2A (PP2A) forms a complex with CaMKIV and negatively regulates its activity. Here we demonstrate that PP2A tightly regulates T200 phosphorylation of endogenous CaMKIV, but has little effect on the phosphorylation of the ectopically-expressed kinase. This differential regulation of endogenous versus exogenous CaMKIV is due to differences in their ability to associate with PP2A, as exogenous CaMKIV associates poorly with PP2A in comparison to endogenous CaMKIV. The inability of exogenous CaMKIV to associate with PP2A appears to be due to limiting amounts of endogenous PP2A regulatory B subunits, since coexpression of Balpha or Bdelta causes the recruitment of PP2Ac to ectopic CaMKIV, leading to formation of a CaMKIV.PP2A complex. Together, these data indicate that the B subunits are essential for the interaction of PP2A with CaMKIV.
Reece
Kelie M
KM
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Mazalouskas
Matthew D
MD
Wadzinski
Brian E
BE
D045163:Antibodies, Phospho-Specific; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D020035:Holoenzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D045163:Antibodies, Phospho-Specific; D020035:Holoenzymes; D021122:Protein Subunits; C517683:CAMK4 protein, human; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D054648:Protein Phosphatase 2