Effect of heparin on phosphorylation site specificity of neuronal Cdc2-like kinase.
Neuronal Cdc2-like kinase (Nclk) can be stimulated by heparin in a substrate-dependent manner. While phosphorylation of tau is markedly enhanced by heparin, phosphorylation of histone H1 by Nclk is essentially unaffected. A histone H1 peptide, HS(9-18): PKTPKKAKKL, and its substitution analogues were used to examine the basis of the differential heparin effect. In the presence of heparin, the phosphorylation site specificity of Nclk is altered and only proline immediately following the phosphorylation site is still an essential substrate determinant. This change in the site specificity may adequately account for the differential heparin effect on histone H1 and tau phosphorylation.
Qi
Z
Z
Department of Medical Biochemistry, University of Calgary, Alta, Canada.
Zhu
X
X
Goedert
M
M
Fujita
D J
DJ
Wang
J H
JH
D000925:Anticoagulants / Q000494:pharmacology*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D006493:Heparin / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D000925:Anticoagulants; D006657:Histones; D010455:Peptides; D016875:tau Proteins; D006493:Heparin; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases