 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 9, 2020-2032, Copyright © 1989 by Society for Neuroscience
Distinct autophosphorylation sites sequentially produce autonomy and inhibition of the multifunctional Ca2+/calmodulin-dependent protein kinase
LL Lou and H Schulman
Department of Pharmacology, Stanford University School of Medicine, California 94305.
The multifunctional Ca2+/calmodulin-dependent protein kinase
(multifunctional CaM kinase) may be an important mediator for
neurotransmitters and hormones that utilize Ca2+ as a "second messenger."
We examined the ability of autophosphorylation to convert the
multifunctional CaM kinase to a Ca2+/calmodulin-independent (autonomous)
form to determine whether autophosphorylation is a mechanism for short- or
long-term enhancement of Ca2+ action. As the kinase incorporates phosphate
during continuous stimulation by Ca2+/calmodulin, its ability to
phosphorylate exogenous substrates becomes increasingly autonomous.
Withdrawal of Ca2+ after a critical level of phosphate incorporation is
reached leads to a "burst" or rapid increase in Ca2+-independent
autophosphorylation. The "burst" of autophosphorylation is distinct from
the initial Ca2+-dependent autophosphorylation, however, since it inhibits
substrate phosphorylation. Both Ca2+-dependent and Ca2+-independent
substrate phosphorylation are inhibited by this autonomous
autophosphorylation. Thus, autophosphorylation has a dual role in
modulating the activity of multifunctional CaM kinase. It initially enables
the kinase to continue phosphorylating substrates after Ca2+ levels
decline, but it eventually suppresses this autonomous activity. Tryptic
phosphopeptide mapping demonstrates that appearance of
phosphothreonine-containing peptides is common to several conditions used
to generate an autonomous enzyme. Sequencing reveals the critical
"autonomy" site to be threonine286. The inhibitory mode of
autophosphorylation involves 3 additional phosphopeptides containing a
serine and a threonine residue.
This article has been cited by other articles:
|
|
|
|
 
J. Si and S. J. Collins
Activated Ca2+/Calmodulin-Dependent Protein Kinase II{gamma} Is a Critical Regulator of Myeloid Leukemia Cell Proliferation
Cancer Res.,
May 15, 2008;
68(10):
3733 - 3742.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Jiang, N. J. Lautermilch, H. Watari, R. E. Westenbroek, T. Scheuer, and W. A. Catterall
Modulation of CaV2.1 channels by Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain
PNAS,
January 8, 2008;
105(1):
341 - 346.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Anderson
Multiple downstream proarrhythmic targets for calmodulin kinase II: Moving beyond an ion channel-centric focus
Cardiovasc Res,
March 1, 2007;
73(4):
657 - 666.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hudmon, H. Schulman, J. Kim, J. M. Maltez, R. W. Tsien, and G. S. Pitt
CaMKII tethers to L-type Ca2+ channels, establishing a local and dedicated integrator of Ca2+ signals for facilitation
J. Cell Biol.,
November 7, 2005;
171(3):
537 - 547.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Griffith
Calcium/Calmodulin-Dependent Protein Kinase II: An Unforgettable Kinase
J. Neurosci.,
September 29, 2004;
24(39):
8391 - 8393.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Griffith
Regulation of Calcium/Calmodulin-Dependent Protein Kinase II Activation by Intramolecular and Intermolecular Interactions
J. Neurosci.,
September 29, 2004;
24(39):
8394 - 8398.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. R. Gaertner, J. A. Putkey, and M. N. Waxham
RC3/Neurogranin and Ca2+/Calmodulin-dependent Protein Kinase II Produce Opposing Effects on the Affinity of Calmodulin for Calcium
J. Biol. Chem.,
September 17, 2004;
279(38):
39374 - 39382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. P. Harvey, S. S. Banga, and H. L. Ozer
Regulation of the Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II by the PP2C Phosphatase PPM1F in Fibroblasts
J. Biol. Chem.,
June 4, 2004;
279(23):
24889 - 24898.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Weeber, Y.-H. Jiang, Y. Elgersma, A. W. Varga, Y. Carrasquillo, S. E. Brown, J. M. Christian, B. Mirnikjoo, A. Silva, A. L. Beaudet, et al.
Derangements of Hippocampal Calcium/Calmodulin-Dependent Protein Kinase II in a Mouse Model for Angelman Mental Retardation Syndrome
J. Neurosci.,
April 1, 2003;
23(7):
2634 - 2644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Bradshaw, A. Hudmon, and H. Schulman
Chemical Quenched Flow Kinetic Studies Indicate an Intraholoenzyme Autophosphorylation Mechanism for Ca2+/Calmodulin-dependent Protein Kinase II
J. Biol. Chem.,
May 31, 2002;
277(23):
20991 - 20998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Shohat, T. Spivak-Kroizman, O. Cohen, S. Bialik, G. Shani, H. Berrisi, M. Eisenstein, and A. Kimchi
The Pro-apoptotic Function of Death-associated Protein Kinase Is Controlled by a Unique Inhibitory Autophosphorylation-based Mechanism
J. Biol. Chem.,
December 7, 2001;
276(50):
47460 - 47467.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Eshete and R. D. Fields
Spike Frequency Decoding and Autonomous Activation of Ca2+-Calmodulin-Dependent Protein Kinase II in Dorsal Root Ganglion Neurons
J. Neurosci.,
September 1, 2001;
21(17):
6694 - 6705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. D. Moody, H. J. Carlisle, and T. J. O'Dell
A Nitric Oxide-Independent and beta -Adrenergic Receptor-Sensitive Form of Metaplasticity Limits theta -Frequency Stimulation-Induced LTP in the Hippocampal CA1 Region
Learn. Mem.,
November 1, 1999;
6(6):
619 - 633.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Makhinson, J. K. Chotiner, J. B. Watson, and T. J. O'Dell
Adenylyl Cyclase Activation Modulates Activity-Dependent Changes in Synaptic Strength and Ca2+/Calmodulin-Dependent Kinase II Autophosphorylation
J. Neurosci.,
April 1, 1999;
19(7):
2500 - 2510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. C. Rich and H. Schulman
Substrate-directed Function of Calmodulin in Autophosphorylation of Ca2+/Calmodulin-dependent Protein Kinase II
J. Biol. Chem.,
October 23, 1998;
273(43):
28424 - 28429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ishida, I. Kameshita, and H. Fujisawa
A Novel Protein Phosphatase That Dephosphorylates and Regulates Ca2+/Calmodulin-dependent Protein Kinase II
J. Biol. Chem.,
January 23, 1998;
273(4):
1904 - 1910.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Matovcik, S. S. Rhee, J. F. Schaefer, and B. K. Kinder
Reconstitution of Calcium-Regulated Parathyroid Hormone Secretion from Streptolysin-O-Permeabilized Parathyroid Cells by Guanosine 5'-O-(Thio)Triphosphate
Endocrinology,
March 1, 1997;
138(3):
1170 - 1179.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Putkey and M. N. Waxham
A Peptide Model for Calmodulin Trapping by Calcium/Calmodulin-dependent Protein Kinase II
J. Biol. Chem.,
November 22, 1996;
271(47):
29619 - 29623.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Chatila, K. A. Anderson, N. Ho, and A. R. Means
A Unique Phosphorylation-dependent Mechanism for the Activation of Ca2+/Calmodulin-dependent Protein Kinase Type IV/GR
J. Biol. Chem.,
August 30, 1996;
271(35):
21542 - 21548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hudmon, J. Aronowski, S. J. Kolb, and M. N. Waxham
Inactivation and Self-association of Ca[IMAGE]/Calmodulin-dependent Protein Kinase II during Autophosphorylation
J. Biol. Chem.,
April 12, 1996;
271(15):
8800 - 8808.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Selbert, K. A. Anderson, Q.-H. Huang, E. G. Goldstein, A. R. Means, and A. M. Edelman
Phosphorylation and Activation of Ca[IMAGE]-Calmodulin-dependent Protein Kinase IV by Ca[IMAGE]-Calmodulin-dependent Protein Kinase Ia Kinase
J. Biol. Chem.,
July 21, 1995;
270(29):
17616 - 17621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. B. McNeill and R. J. Colbran
Interaction of Autophosphorylated Ca[IMAGE]/Calmodulin-dependent Protein Kinase II with Neuronal Cytoskeletal Proteins
J. Biol. Chem.,
April 28, 1995;
270(17):
10043 - 10049.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ishida and H. Fujisawa
Stabilization of Calmodulin-dependent Protein Kinase II through the Autoinhibitory Domain
J. Biol. Chem.,
February 3, 1995;
270(5):
2163 - 2170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Meyer, P. I. Hanson, L. Stryer, and H. Schulman
Calmodulin Trapping by Calcium-Calmodulin-Dependent Protein Kinase
Science,
May 22, 1992;
256(5060):
1199 - 1202.
[Abstract]
[PDF]
|
|
|
|
|
