SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1

Abstract

Arginine/serine protein kinases constitute a novel class of enzymes that can modify arginine/serine (RS) dipeptide motifs. SR splicing factors that are essential for pre-mRNA splicing are among the best characterized proteins that contain RS domains. TwoSRprotein-specifickinases, SRPK1 and SRPK2, have been considered as highly specific for the phosphorylation of these proteins, thereby contributing to splicing regulation. However, despite the fact that SR proteins are more or less conserved among metazoa and have a rather ubiquitous tissue distribution we now demonstrate that SRPK1 is predominantly expressed in testis. In situ expression analysis on transverse sections of adult mouse testis shows that SRPK1 mRNA is abundant in all germinal cells but not in mature spermatozoa. RS kinase activity was found primarily in the cytosol and only minimal activity was detected in the nucleus. In a search for testis-specific substrates of SRPK1 we found that the enzyme phosphorylates human protamine 1 as well as a cytoplasmic pool of SR proteins present in the testis. Protamine 1 belongs to a family of small basic arginine-rich proteins that replace histones during the development of mature spermatozoa. The result of this progressive replacement is the formation of a highly compact chromatin structure devoid of any transcriptional activity. These findings indicate that SRPK1 may have a role not only in pre-mRNA splicing, but also in the condensation of sperm chromatin.

Serological identification of adult T‐cell leukaemia‐associated antigens

“…From the published literature, LIMS1 (Braun et al, 2003) and PPFIBP1 (Serra-Pages et al, 1998) genes were widely expressed in normal human tissues by Northern blot analysis. In contrast, SRPK1 (Papoutsopoulou et al, 1999) and LIAS (Ito et al, 2004) were reported to have restricted tissue expression and to have a cancer-testis-like profile. Thus, we focused on SRPK1 and LIAS for further studies.…”

The Yeast Genes ROX1, IXR1, SKY1 and Their Effect upon Enzymatic Activities Related to Oxidative Stress

“…Besides, ∆sky1 cells display a mutator phenotype, which suggests that Sky1 might play a significant role in specific DNA repair pathways (Schenk et al, 2002). SRPK1, the human homologue of Sky1, is predominantly found in the testis, where it phosphorylates protamine 1 as well as a cytoplasmic pool of other SR proteins (Papoutsopoulou et al, 1999). Protamines are small highly basic proteins that replace histones during spermatogenesis, resulting in extreme chromatin condensation (Oliva & Dixon, 1991).…”

Targeting the RNA Splicing Machinery as a Novel Treatment Strategy for Pancreatic Carcinoma

“…Once phosphorylated, SR proteins are believed to influence the selection of splice sites by mediating the interactions between nascent transcripts and components of the spliceosomal machinery (14). SRPK1 has been shown by Northern analysis to have a ubiquitous expression pattern among tissues, although the highest transcript levels exist in testis and pancreas (13,15). Presently, the location and function of the SRPK1 protein within the pancreas remains unknown.…”

“…Presently, the location and function of the SRPK1 protein within the pancreas remains unknown. Studies have shown a dual role for SRPK1 in testicular germ cells where, besides its role regulating splice factors, this kinase phosphorylates the SR domain-containing protein protamine 1 to effect a more compact condensation of chromatin during spermatogenesis (15).…”