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PMID: 9059986 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Potentiation of GSK-3-catalyzed Alzheimer-like phosphorylation of human tau by cdk5.

Molecular and cellular biochemistry ·Vol. 167 ·No. 1-2 ·1997-02-00 ·Pages 99-105

Sengupta A, Wu Q, Grundke-Iqbal I, Iqbal K, Singh TJ

Abstract

Tau protein from Alzheimer disease (AD) brain is hyperphosphorylated by both proline-dependent protein kinases (PDPKs) and non-PDPKs. It is presently unclear how PDPKs and non-PDPKs interact in tau hyperphosphorylation. Previously we have shown that non-PDPKs can positively modulate the activity of a PDPK (GSK-3) in tau phosphorylation (Singh et al. (1995) FEBS Lett. 358, 267-272). In this study we have investigated whether (A) non-PDPKs can also modulate the activity of the PDPK, cdk5, (B) a PDPK can modulate the activities of another PDPK, as well as non-PDPKs. We found that, like GSK-3, the activity of cdk5 is stimulated if tau were first prephosphorylated by any of several non-PDPKs (A-kinase, C-kinase, CK-1, CaM-kinase II). Prephosphorylation of tau by cdk5 stimulated both the rate and extent of a subsequent phosphorylation catalyzed by GSK-3. Under these conditions thr 231 phosphorylation was especially enhanced (9-fold). No significant stimulation of phosphorylation was observed when the order of these kinases was reversed (i.e. GSK-3 followed by cdk5). By contrast, prephosphorylation of tau by cdk5 served to inhibit subsequent phosphorylation catalyzed by C-kinase and CK-1, but not by A-kinase or CaM-kinase II. Our results suggest that in tau hyperphosphorylation in AD brain, cdk5-catalyzed phosphorylation may serve to upregulate the activity of GSK-3 and down-regulate the activities of C-kinase and CK-1.

MeSH Terms
Alzheimer Disease/metabolism Antibodies/metabolism Binding Sites Calcium-Calmodulin-Dependent Protein Kinases/metabolism Casein Kinases Cyclic AMP-Dependent Protein Kinases/metabolism Cyclin-Dependent Kinase 5 Cyclin-Dependent Kinases Epitopes Glycogen Synthase Kinase 3 Humans Phosphorylation Protein Kinases/metabolism Protein Serine-Threonine Kinases/metabolism tau Proteins/immunology,metabolism
Chemicals
Antibodies Epitopes tau Proteins Protein Kinases calcium-dependent protein kinase Casein Kinases Cyclin-Dependent Kinase 5 Protein Serine-Threonine Kinases Cyclic AMP-Dependent Protein Kinases Calcium-Calmodulin-Dependent Protein Kinases CDK5 protein, human Cyclin-Dependent Kinases Glycogen Synthase Kinase 3
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sengupta A
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
Wu Q
Grundke-Iqbal I
Iqbal K
Singh T J
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Article Info
Journal
Molecular and cellular biochemistry
Abbr.
Mol Cell Biochem
ISSN
0300-8177
DOI
10.1023/a:1006883924775
Published
1997-02-00
Pages
99-105
Language
English
Region
Netherlands
NLM ID
0364456
Subset
IM
Grants
NIA NIH HHS · AG05892 · United States
NIA NIH HHS · AG08076 · United States
NINDS NIH HHS · NS18105 · United States
External Links
PubMed source DOI: 10.1023/a:1006883924775 View journal details
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