Ca2+-Calmodulin Tubulin Kinase System and its Role in Mediating the Ca2+ Signal in Brain

DeLorenzo, Robert J.; Gonzalez, B.; Goldenring, James R.; Bowling, Allen C.; Jacobson, R.D.

doi:10.1016/s0079-6123(08)63779-6

Cited by 18 publications

(8 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of course, an increase in soluble proteins available for phos- The 55K doublet from the brains of hens paralyzed by TOCP, which is so highly phosphorylated in the presence of Ca2+, does comigrate on onedimensional SDS-PAGE with purified bovine-and @tubulin (provided by Dr. Richard D. Irwin). De-Lorenzo and co-workers (DeLorenzo and Freedman, 1977;DeLorenzo, 1980;DeLorenzo et al, 1982;Delorenzo, 1981, 1982a,b) have observed the formation of twisted filamentous polymers consequent to the endogenous Ca2+-and CaM-dependent phosphorylation of rat brain synaptoplasmic tubulin. These polymers are distinct from either microtubules or tubulin ribbons or sheets.…”

Section: Discussionmentioning

confidence: 98%

Changes in In Vitro Brain and Spinal Cord Protein Phosphorylation After a Single Oral Administration of Tri‐o‐Cresyl Phosphate to Hens

Patton

Lapadula

O’Callaghan

et al. 1985

Journal of Neurochemistry

View full text Add to dashboard Cite

The effect of a single oral 750 mg/kg dose of tri-o-cresyl phosphate (TOCP) on the endogenous phosphorylation of brain and spinal cord proteins was assessed in hens during the development of and recovery from delayed neurotoxicity. Crude membrane and cytosolic fractions were prepared from the brains and spinal cords of control and TOCP-treated hens at 1, 7, 14, 21, 35, and 55 days after treatment. Brain and spinal cord protein phosphorylation with [gamma-32P]ATP was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), autoradiography, and microdensitometry. TOCP administration conferred calcium and calmodulin dependence on the phosphorylation of a few brain cytosolic proteins and caused an increase in the phosphorylation of a number of other cytosolic and membrane proteins. This effect of TOCP was large in magnitude, and its time course reflected the onset of and recovery from the signs of ataxia and paralysis associated with delayed neurotoxicity in the hen. The molecular weights (Mr) and maximal phosphorylation (percent of control) for the most prominently affected bands were as follows: brain cytosol--50K (183%), 55K (575%), 60K (529%), 65K (273%), and 70K (548%); brain membranes--50K (622%) and 60K (697%); and spinal cord cytosol--20K (182%). The role of endogenous phosphorylation reactions in and their potential usefulness as biochemical indicators of delayed neurotoxicity are being explored further.

show abstract

Section: Discussionmentioning

confidence: 98%

Changes in In Vitro Brain and Spinal Cord Protein Phosphorylation After a Single Oral Administration of Tri‐o‐Cresyl Phosphate to Hens

Patton

Lapadula

O’Callaghan

et al. 1985

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Calmodulin (CaM) is an effector of calcium signaling and has a central role in neurodegenerative processes such as plasticity, learning, and memory (Klee et al, 1980;Sola et al, 1999). CaM participates in synaptic function and neurotransmitter release, playing a role in Ca 21 -stimulated phosphorylation of synaptic proteins (Delorenzo et al, 1982). In addition, CaM regulates the assembly and disassembly of microtubules (Marcum et al, 1978).…”

Section: Calcium Signaling Proteinsmentioning

confidence: 99%

The wheat germ agglutinin‐fractionated proteome of subjects with Alzheimer's disease and mild cognitive impairment hippocampus and inferior parietal lobule: Implications for disease pathogenesis and progression

Domenico

Owen

Sultana

et al. 2010

J of Neuroscience Research

View full text Add to dashboard Cite

Lectin affinity chromatography is a powerful separation technique that fractionates proteins by selectively binding to specific carbohydrate moieties characteristic of protein glycosylation type. Wheat germ agglutinin (WGA) selectively binds terminal N-acetylglucosamine (O-GlcNAc) and sialic acid moieties characteristic of O-linked glycosylation. The current study utilizes WGA affinity chromatography to fractionate proteins from hippocampus and inferior parietal lobule (IPL) from subjects with Alzheimer's disease (AD) and arguably its earliest form, mild cognitive impairment (MCI). Proteins identified by proteomics that were fractionated from MCI and AD hippocampus by WGA affinity chromatography with altered levels compared with age-matched controls included GP96, γ-enolase, glutamate dehydrogenase, glucosidase IIα, 14-3-3ϵ, 14-3-3γ, 14-3-3ζ, tropomyosin-2, calmodulin 2, gelsolin, β-synuclein, α1-antichymotrypsin, and dimethylguanosine tRNA methyltransferase. Proteins identified by proteomics that were fractionated from MCI and AD IPL by WGA affinity chromatography showing altered levels compared with age-matched controls included protein disulfide isomerase, calreticulin, and GP96. The proteins described in this study are involved in diverse processes, including glucose metabolism, endoplasmic reticulum (ER) functions, chaperoning, cytoskeletal assembly, and proteolysis, all of which are affected in AD. This study, the first to use proteomics to identify WGA-fractionated proteins isolated from brains from subjects with MCI and AD, provides additional information about the active proteome of the brain throughout AD progression.

show abstract

“…CaM kinase I1 modulates neurotransmitter synthesis and release (6-9), receptor-gated ion channels (10, 11) calciumdependent ion currents (12,13), and neuroskeletal elements (14,15). Therefore, inhibition of this enzyme would have significant effects on neuronal function.…”

mentioning

confidence: 99%

Bilirubin Induces a Calcium-Dependent Inhibition of Multifunctional Ca2+/Calmodulin-Dependent Kinase II Activity in Vitro

1995

View full text Add to dashboard Cite

Excessive bilirubin levels in newborn infants result in longterm neurologic deficits that remain after bilirubin levels return to normal. Much of the observed neurologic deficits can be attributed to bilirubin-induced, delayed neuronal cell death. Inhibition of calcium/calmodulin-dependent kinase I1 (CaM kinase 11) activity that precedes cell death is observed in conditions such as seizure activity, stroke, and glutamate excitotoxicity. Because neonatal bilirubin exposure results in neuronal loss in developing brain systems, we tested whether bilirubin exposure would induce an immediate inhibition of CaM kinase I1 activity, in vitro. P-81 filtration assay of basal and calcium-stimulated kinase activity was performed under standard kinase assay conditions. Bilirubin and/or albumin was added to the reaction vessels to determine the effect of these agents on kinase activity. Bilirubin exposure resulted in a concentration-dependent inhibition of CaM kinase I1 activity (IC,, = 16.78 pM). At concentrations above 50 pM, bilirubin exposure resulted in a 71 ? 8% (mean ? SD) inhibition of kinase activity (p < 0.001, t test, n = 10).Bilirubin exposure did not result in kinase inhibition if excessive bilirubin was removed by albumin binding before stimulation of kinase activity (106.9 ? 9.6% control activity, n = 5). However, removal of bilirubin by binding with albumin after calcium addition did not restore kinase activity. (36.1 5 3.8% control activity, n = 5). Thus, once inhibition was observed, the activity could not be restored by addition of albumin. The data suggest that bilirubin exposure resulted in a calcium-dependent inhibition of CaM kinase I1 activity that, once induced, was not reversible by removing bilirubin by the addition of albumin. Because inhibition of CaM kinase I1 activity has been correlated with delayed neuronal cell death in many neuropathologic conditions, bilirubin-induced inhibition of this enzyme may be a cellular mechanism by which bilirubin exposure results in delayed neuronal cell death in developing brain. (Pediatr Res 38: 949-954, 1995) Abbreviation CaM kinase 11, calcium/calmodulin-dependent kinase I1

show abstract

Ca2+-Calmodulin Tubulin Kinase System and its Role in Mediating the Ca2+ Signal in Brain

Cited by 18 publications

References 49 publications

Changes in In Vitro Brain and Spinal Cord Protein Phosphorylation After a Single Oral Administration of Tri‐o‐Cresyl Phosphate to Hens

Changes in In Vitro Brain and Spinal Cord Protein Phosphorylation After a Single Oral Administration of Tri‐o‐Cresyl Phosphate to Hens

The wheat germ agglutinin‐fractionated proteome of subjects with Alzheimer's disease and mild cognitive impairment hippocampus and inferior parietal lobule: Implications for disease pathogenesis and progression

Bilirubin Induces a Calcium-Dependent Inhibition of Multifunctional Ca2+/Calmodulin-Dependent Kinase II Activity in Vitro

Contact Info

Product

Resources

About