Disease relevance of Kin

• The S49 mouse lymphoma mutant cell line Kin- is resistant to the cytotoxic effects of elevated cAMP levels, has no detectable cAMP-dependent protein kinase activity, and has depressed levels of cAMP-binding regulatory subunits [1].

High impact information on Kin

• In addition to having catalytic activity, the C alpha subunit from Kin- cells is inhibited in the presence of mouse RI alpha regulatory subunit, indicating that formation of the holoenzyme complex is normal [1].
• We suggest that the mutation responsible for the Kin- phenotype is in a cellular component that directly or indirectly causes Kin- catalytic subunit protein to be degraded rapidly [1].
• Poly(A+) RNA was isolated from Y1 and Kin mutant cells and was translated in a cell-free, reticulocyte lysate system in the presence of L-[35S]methionine [2].
• A series of mutant cell lines (Kin) were previously isolated from Y1 adrenocortical tumor cells based on their ability to resist the growth-inhibitory effects of 8-bromo cAMP [3].
• These observations indicate that the cAMP-resistant phenotype of Kin mutant clones resulted specifically from single mutational events in RI and thus establish the importance of cAMPdPK as an essential regulator of adrenocortical function [3].

Biological context of Kin

• We cloned the C alpha cDNA from Kin- cells and show that its transient expression in another cell type leads to activation of a cAMP-sensitive luciferase reporter gene, suggesting that functional C alpha protein is made [1].
• The -170 element was 25-fold more effective in enhancing gene expression from the reporter construct in Y1 cells than in Kin mutant cells; the elements at -65, -140, and -210 were 3-fold more effective in Y1 cells than in Kin mutant cells; the -280 element was equally effective in the parent and Kin mutant clones [4].
• Expression of Kin, a nuclear protein binding to curved DNA, in mammal and avian brains [5].
• In conclusion, the expression of the Kin protein is preserved in the phylogeny of the brain of higher vertebrates [5].
• The distribution of Kin protein, the vertebrate homologue of the bacterial recA nuclear protein involved in illegitimate recombinant DNA repair and gene regulation, was analysed in the brain of the mouse, quail, turtle and frog by immunocytochemical methods [6].

Anatomical context of Kin

• The S49 Kin- cell line transcribes and translates a functional mRNA coding for the catalytic subunit of cAMP-dependent protein kinase [1].
• Apparent penetration of cyclosporin A into the cerebrospinal fluid (CSF) determined with the intravenous bolus injection technique is small with a Kin of 0.79 +/- 0.07 microliter g-1 min-1 [7].
• Brain perfusion studies in the guinea pig produce a unidirectional cerebrovascular permeability constant (Kin) of 1.2 +/- 0.28 microliter g-1 min-1 for the hippocampus [7].
• It is also shown that whatever the species examined, Kin protein is consistently more highly expressed in those regions of the brain with a conservative evolutionary history (e.g. the olfactory and limbic systems, the hypothalamus, the monoaminergic system, the cerebellum, and the nuclei of sensory and motor cranial nerves) [6].

Associations of Kin with chemical compounds

• Studies on the conversion of 22(R)-hydroxycholesterol into steroid products in parent and mutant cells indicate that the Kin mutations reduce the steroidogenic capacity of the cell as well as inhibit the hormone- and cyclic nucleotide-dependent mobilization of substrate cholesterol [8].
• Molecular basis for the 3',5'-cyclic adenosine monophosphate resistance of Kin mutant Y1 adrenocortical tumor cells [3].
• The Kin 8 cell line is derived from Y1 cells and harbours a defect in the cyclic AMP (cAMP)-dependent protein kinase, making it refractory to cAMP-dependent regulation of several enzymes [9].
• Three different forms of glutathione transferase (GST) have been resolved in the two mouse adrenal tumour cell lines Y1 and Kin 8 [9].
• C2 toxin treatment of a protein kinase A mutant Y-1 cell (Kin 8) resulted in morphological changes and an increase in steroid output that was not different from that observed for wild type Y-1 cells [10].

Other interactions of Kin

• We demonstrate that although the Kin- cell line lacks detectable catalytic subunit protein, these cells express wild-type levels of mRNA for both C alpha and C beta catalytic subunit isoforms [1].
• These results strongly support the hypothesis that impaired expression of steroidogenic enzymes in the Kin mutants results directly from defects in cAMP-dependent protein kinase activity [11].
• Also, the steady-state levels of mGTmu1 mRNA were much lower in Y1 cells treated with forskolin (which activates adenylate cyclase) compared with control cells, but there was no difference in mGTmu1 mRNA levels between control and forskolin-treated Kin 8 cells [9].
• Cytochalasin E also caused induction of plasminogen activation in Y1, but not in Kin 2 or Kin 8 cells [12].

Analytical, diagnostic and therapeutic context of Kin

• Using immunocytochemistry with anti-RecA antibodies, we report the ubiquitous presence of the Kin protein in the CNS of mice and quails [5].

References