Murine NIMA-related kinases are expressed in patterns suggesting distinct functions in gametogenesis and a role in the nervous system

Abstract

NIMA protein kinase is a major regulator of progression into mitosis in Aspergillus nidulans. Dominant negative forms of NIMA protein prevent entrance into mitosis in HeLa cells, suggesting that mammals have a similar pathway. We have reported previously the isolation of a murine NIMA-related kinase, designated Nek1, and more recently several additional NIMA-related human kinases have been cloned. The existence of several mammalian NIMA-related genes raises the questions of whether the di erent mammalian members have redundant, overlapping or distinct functions, and whether these functions are related to the role of NIMA in controlling mitosis. To address these questions we have studied the expression patterns of the di erent murine nek genes. To this end, we isolated a murine nek2 cDNA and compared its patterns of expression, during both gametogenesis and embryogenesis, to those of nek1. Both genes were highly expressed in developing germ cells, albeit in distinct patterns. In both females and males, nek1 is expressed much earlier than nek2, suggesting only limited ability for functional redundancy. Surprisingly, a striking speci®city of nek1 expression was found: high levels of nek1 RNA were observed in distinct regions of the nervous system, most notably in neurons of the peripheral ganglia. These patterns suggest that the di erent mammalian NIMA-related kinases participate in di erent phases of the meiotic process and may also have functions other than cell cycle control.

Cloning and Characterization of the Murine Nek3 Protein Kinase, a Novel Member of the NIMA Family of Putative Cell Cycle Regulators

“…For comparison, the left-hand panel shows the protein profiles of these samples, as revealed by Coomassie Blue staining, confirming equal loading. The right-hand panel shows the results of probing the same samples with antibodies against Nek2, one of the Neks shown previously to be expressed predominantly in testis (22)(23)(24). From these data it is clear that Nek3 is expressed at comparable levels in both testis and intestine, in striking contrast to Nek2.…”

“…Nek2 localizes to the centrosome, and overexpression of active Nek2 profoundly affects centrosome structure in cultured cells. Nek2 is highly expressed in testis (22)(23)(24), and the same is true for Nek1 (15). Interestingly, however, Nek1 and Nek2 display different expression patterns during spermatogenesis, suggesting that they may perform distinct functions.…”

“…This result was confirmed also by comparing the amounts of mNek3 protein present in intestine and testis. It is clear, therefore, that the organ specificity of mNek3 expression differs very markedly from that of Nek1 and Nek2, both of which were recently shown to be expressed to far higher levels in the germ lines than in any other mammalian tissue (15,(22)(23)(24).…”

“…This latter result is in striking contrast to data reported previously for murine Nek1 and Nek2. Both of these kinases are in fact highly expressed in testis, although their precise expression patterns during spermatogenesis differ (15,(22)(23)(24).…”

Transcriptome analysis of differentiating spermatogonia stimulated with kit ligand

“…A kinase possibly involved early in the DNA damage response. In the testis is expressed at the beginning of the meiotic phase (Arama et al, 1998;Letwin et al, 1992 (Shao et al, 2001) Spermatogonial markers 1428639_at 0.58 Lin9 Required for the expression of the spermatogonial marker B-Myb (Latham et al, 1996;Pilkinton et al, 2007) 1422655_at 0.57 Ptch2 Patched homolog 2. A receptor for sonic hedgehog, expressed in spermatogonia, and at lower levels in spermatocytes (Szczepny et al, 2006) [no specific references are given for these genes, since description of their metabolic function can be found in the free databases at the link http://www.informatics.jax.org].…”