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The receptor‐associated protein (RAP) binds calmodulin and is phosphorylated by calmodulin‐dependent kinase II.
Author(s) -
Petersen C. M.,
Ellgaard L.,
Nykjaer A.,
Vilhardt F.,
Vorum H.,
Thøgersen H. C.,
Nielsen M. S.,
Jacobsen C.,
Moestrup S. K.,
Gliemann J.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00791.x
Subject(s) - calmodulin , university hospital , library science , medicine , biology , biochemistry , family medicine , computer science , enzyme
The receptor‐associated protein, RAP, is an intracellular protein that may function as a chaperone for the LDL‐receptor family receptors. Here we report calmodulin as the first identified RAP binding protein outside of the LDL‐receptor family members. We demonstrate that RAP binds calmodulin in a Ca2+‐ and pH‐dependent manner characteristic of calmodulin‐dependent enzymes, and present evidence that RAP is a substrate for calmodulin‐dependent enzymes. Thus, CaM‐kinase II and calcineurin readily phosphorylate and dephosphorylate, respectively, serine residues in RAP, and in the individual RAP domains D2 (amino acids 113–218) and D3 (amino acids 219–323) which both contain sites for CaM‐kinase II‐mediated phosphorylation and for calmodulin binding. In addition, we provide evidence that RAP is phosphorylated by other kinases such as casein kinase II. Studies of 32[ortho]P‐labelled cell cultures demonstrate that RAP is phosphorylated in vivo. Our results suggest that RAP may have hitherto unknown functions implicating phosphorylation and calmodulin‐mediated modulation.