| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-164 |
Sentence |
denotes |
Characterization of the mechanism of regulation of Ca2+/ calmodulin-dependent protein kinase I by calmodulin and by Ca2+/calmodulin-dependent protein kinase kinase. |
| T2 |
165-369 |
Sentence |
denotes |
Ca2+/calmodulin-dependent protein kinase I (CaMKI) is maintained in an autoinhibited state by the interaction of a COOH-terminal helix-loop-helix (Ile286-Met316) regulatory domain with the catalytic core. |
| T3 |
370-508 |
Sentence |
denotes |
Activation of the enzyme by calmodulin (CaM) also allows CaMKI to be phosphorylated and activated by a second enzyme, CaMK kinase (CaMKK). |
| T4 |
509-757 |
Sentence |
denotes |
To more thoroughly characterize the regulation of CaMKI by CaM and its interrelationship with phosphorylation by CaMKK, we have carried out a detailed structure-function analysis using recombinant wild-type (WT) and mutant forms of CaMKI and CaMKK. |
| T5 |
758-932 |
Sentence |
denotes |
CaMKI-WT, in the absence of CaM, or CaMKI-299 and CaMKI-298 were autoinhibited and could not be phosphorylated by CaMKK-433 (a truncated constitutively active form of CaMKK). |
| T6 |
933-1052 |
Sentence |
denotes |
Removal of Phe298 (CaMK-297) generated a constitutively active form of CaMKI that was also phosphorylated by CaMKK-433. |
| T7 |
1053-1158 |
Sentence |
denotes |
CaMKI-WT was essentially inactive in the absence of CaM (K0.5 for activation by CaM approximately 30 nM). |
| T8 |
1159-1256 |
Sentence |
denotes |
Mutation of Ile294 and Phe298 to alanine (CaMKI-2A) resulted in measurable basal enzyme activity. |
| T9 |
1257-1350 |
Sentence |
denotes |
Additional mutation of Ile286 and Val290 to alanine (CaMKI-4A) increased this basal activity. |
| T10 |
1351-1526 |
Sentence |
denotes |
Mutation of Trp303 (CaMKI-W303S) resulted in a large increase in the K0.5 for CaM ( approximately 100 microM), supporting a role for this residue as an initial target for CaM. |
| T11 |
1527-1667 |
Sentence |
denotes |
Mutation of Phe307 (CaMKI-F307A) resulted in increased basal enzyme activity, supporting a role for this residue in autoinhibition of CaMKI. |
| T12 |
1668-1839 |
Sentence |
denotes |
Together these studies demonstrate the critical role of specific amino acids in the autoinhibition of CaMKI and also in its activation by CaM and phosphorylation by CaMKK. |
