Linked Life Data

17696464

Source:http://linkedlifedata.com/resource/pubmed/id/17696464

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-9-7
pubmed:abstractText
Protein conformational changes due to cofactor binding (e.g., metal ions, heme) and/or post-translational modifications (e.g., phosphorylation) modulate dynamic protein complexes. Calmodulin (CaM) plays an essential role in regulating calcium signaling and homeostasis. Herein, we report a straightforward and systematic approach to identify potential calcium- and phosphorylation-dependent CaM complexes in a proteome-wide manner. We have identified over 120 CaM-associated proteins encompassing four different classes of CaM binding in HeLa cells, namely, calcium-dependent and phosphorylation-dependent (e.g., EDD1), calcium-dependent and phosphorylation-independent (e.g., myosin IE), calcium-independent and phosphorylation-dependent (e.g., DDX3), and calcium-independent and phosphorylation-independent (e.g., DDX5). To demonstrate the utility of our method in understanding biological pathways, we showed that in vivo phosphorylation of inositol 1,4,5-triphosphate receptor type 1 (IP3R1) at Ser1598 significantly reduced the affinity of its Ca2+-dependent CaM binding. However, phosphorylation of IP3R1 did not substantially affect its Ca2+-independent CaM binding. These results shed new lights on the mechanism underlying the marked increase of Ca2+ release due to IP3R1 phosphorylation. We further showed that staurosporine-sensitive kinase(s) and phosphatase PP1 play a critical role in modulating the phosphorylation-dependent CaM binding of IP3R1. Our method may serve as a general strategy to identify and characterize phosphorylation-dependent protein complexes, to pinpoint the phosphorylation sites and associated kinase(s) and phosphatase(s) involved in the protein-protein interactions, and to functionally characterize these complexes in mammalian cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-amino-5-(4-methylphenyl)-7-(tert-b..., http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin, http://linkedlifedata.com/resource/pubmed/chemical/DEAD-box RNA Helicases, http://linkedlifedata.com/resource/pubmed/chemical/Ddx5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate..., http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles, http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines, http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1535-3893
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3718-28
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Proteomic and biochemical studies of calcium- and phosphorylation-dependent calmodulin complexes in Mammalian cells.
pubmed:affiliation
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 84-171, Berkeley, California 94720, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.