Elsevier

Genomics

Volume 44, Issue 2, 1 September 1997, Pages 179-187
Genomics

Regular Article
Structure, Expression, and Chromosomal Localization of Human GAK

https://doi.org/10.1006/geno.1997.4873Get rights and content

Abstract

We previously cloned a rat cDNA encoding GAK, an association partner of cyclin G and CDK5. Here, we report the cloning of a cDNA encoding human GAK (1311 amino acids) and show that all of the unique motifs that characterize rat GAK, such as the presence of a Ser/Thr kinase domain, a tensin/auxilin homologous domain, and a Tyr phosphorylation target site, are conserved. The expression profiles of GAK and cyclin G during the synchronized HeLa cell cycle showed that GAK expression oscillates slightly, peaking at G1 phase, although the histone H1 kinase activity remains constant throughout the cell cycle. We also found that the kinase activity of immunoprecipitates of anti-cyclin G antibody fluctuates during the cell cycle with a peak at G1 phase, although the expression level of cyclin G remains almost constant. Northern blot analysis showed that GAK is expressed ubiquitously, with the highest level of expression being observed in the testis. By the FISH technique, we assigned the chromosomal localization of GAK to 4p16.

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      However, the PARK16 loci were not risk factors for PD in this population. PARK17, encoding a serine/threonine kinase GAK, is involved in cell cycle control [21], and in maintenance of microtubule growth around the chromosome during spindle formation [22]. A GWAS study in Caucasian familial patients identified rs11248051 in the PARK17/GAK region as a strong SNP associated with PD (OR 1.70; p = 5.2 × 10−6) [11], which was later confirmed in a large cohort of American PD patients and controls (OR 1.32; p = 3.1 × 10−4) [6].

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    Sequence data from this article have been deposited with the DDBJ/EMBL/GenBank Data Libraries under Accession No. D88435.

    1

    To whom correspondence should be addressed. Telephone: 81-6-875-3980. Fax: 81-6-875-5192. E-mail: [email protected].

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