Cloning and characterization of a testis and brain-specific isoform of mouse 3′-phosphoinositide-dependent protein kinase-1, mPDK-1β

Dong, Lily Q.; Ramos, Fresnida J.; Wick, Michael J.; Lim, Mei Ann; Guo, Zhongmao; Strong, Randy; Richardson, Arlan; Liu, Feng

doi:10.1016/s0006-291x(02)00449-7

Cited by 11 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thomas et al (2005) further reported that a few 3-4-kb Sp1 transcripts, all with a truncated 39 UTR, were detected in a pachytene cDNA library. More examples similar to Sp1 include Rnf4, Nr6a1, Snon2, Pdpk1, and Tsn (Gu et al 1998;Dong et al 2002;Pero et al 2003;Yang et al 2003;Itman et al 2009). For CDS-PRMRs, the truncated exons did not locate in the CDSs preferentially.…”

Section: Discussionmentioning

confidence: 99%

piRNA profiling during specific stages of mouse spermatogenesis

Gan

Lin²,

Zhang³

et al. 2011

RNA

111

View full text Add to dashboard Cite

PIWI-interacting RNAs (piRNAs) are a class of small RNAs abundantly expressed in animal gonads. piRNAs that map to retrotransposons are generated by a ''ping-pong'' amplification loop to suppress the activity of retrotransposons. However, the biogenesis and function of other categories of piRNAs have yet to be investigated. In this study, we first profiled the expression of small RNAs in type A spermatogonia, pachytene spermatocytes, and round spermatids by deep sequencing. We then focused on the computational analysis of the potential piRNAs generated in the present study as well as other published sets. piRNAs mapping to retrotransposons, mRNAs, and intergenic regions had different length distributions and were differentially regulated in spermatogenesis. piRNA-generating mRNAs (PRMRs), whose expression positively correlated with their piRNA products, constituted one-third of the protein-coding genes and were evolutionarily conserved and enriched with splicing isoforms and antisense transcripts. PRMRs with piRNAs preferentially mapped to CDSs and 39 UTRs partitioned into three clusters differentially expressed during spermatogenesis and enriched with unique sets of functional annotation terms related to housekeeping activities as well as spermatogenesis-specific processes. Intergenic piRNAs were divided into 2992 clusters probably representing novel transcriptional units that have not been reported. The transcripts of a large number of genes involved in spermatogenesis are the precursors of piRNAs, and these genes are intricately regulated by alternative splicing and antisense transcripts. piRNAs, whose regulatory role in gene expression awaits to be identified, are clearly products of a novel regulatory process that needs to be defined.

show abstract

Section: Discussionmentioning

confidence: 99%

piRNA profiling during specific stages of mouse spermatogenesis

Gan

Lin²,

Zhang³

et al. 2011

RNA

111

View full text Add to dashboard Cite

show abstract

“…To further confirm that PDK-1 nuclear localization is increased in PTEN Ϫ/Ϫ cells, lysates from PTEN ϩ/ϩ and PTEN Ϫ/Ϫ cells were fractionated into cytoplasmic and nuclear fractions, and the localization of endogenous mPDK-1 was detected by using a rabbit polyclonal anti-PDK-1 antibody (27). As shown in Fig.…”

Section: Pdk-1 Nuclear Translocation Is Regulated By the Pi3-kinase Pmentioning

confidence: 94%

“…2 A and B). We also examined the nuclear localization of mPDK-1␤, a splice variant of PDK-1 that lacks 27 aa at its N terminus (27). The nuclear localization frequency of this PDK-1 isoform is even higher compared with that of mPDK-1␣ (Fig.…”

Section: Pdk-1 Nuclear Translocation Is Regulated By the Pi3-kinase Pmentioning

confidence: 99%

Nuclear translocation of 3′-phosphoinositide-dependent protein kinase 1 (PDK-1): A potential regulatory mechanism for PDK-1 function

Lim

Kikani

Wick

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

3-Phosphoinositide-dependent protein kinase 1 (PDK-1) phosphorylates and activates members of the AGC protein kinase family and plays an important role in the regulation of cell survival, differentiation, and proliferation. However, how PDK-1 is regulated in cells remains elusive. In this study, we demonstrated that PDK-1 can shuttle between the cytoplasm and nucleus. Treatment of cells with leptomycin B, a nuclear export inhibitor, results in a nuclear accumulation of PDK-1. PDK-1 nuclear localization is increased by insulin, and this process is inhibited by pretreatment of cells with phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. Consistent with the idea that PDK-1 nuclear translocation is regulated by the PI3-kinase signaling pathway, PDK-1 nuclear localization is increased in cells deficient of PTEN (phosphatase and tensin homologue deleted on chromosome 10). Deletion mapping and mutagenesis studies unveiled that presence of a functional nuclear export signal (NES) in mouse PDK-1 located at amino acid residues 382 to 391. Overexpression of constitutively nuclear PDK-1, which retained autophosphorylation at Ser-244 in the activation loop in cells and its kinase activity in vitro, led to increased phosphorylation of the predominantly nuclear PDK-1 substrate p70 S6K␤I. However, the ability of constitutively nuclear PDK-1 to induce anchorage-independent growth and to protect against UV-induced apoptosis is greatly diminished compared with the wildtype enzyme. Taken together, these findings suggest that nuclear translocation may be a mechanism to sequestrate PDK-1 from activation of the cytosolic signaling pathways and that this process may play an important role in regulating PDK-1-mediated cell signaling and function.T he 3Ј-phosphoinositide-dependent protein kinase-1 (PDK-1) is a 64-kDa protein comprised of a Ser͞Thr kinase domain near the N terminus and a C-terminal pleckstrin homology (PH) domain (1). This pivotal kinase plays a crucial role in mediating signal transduction downstream of phosphatidylinositol 3-kinase (PI3-kinase) in response to mitogen stimulation. Growth factor stimulation activates PI3-kinase, which converts phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P 2 ] to phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P 3 ]. This lipid product is bound by the PH domain of PDK-1, resulting in the recruitment of PDK-1 to the plasma membrane. Protein kinase B (PKB), the best characterized substrate of PDK-1, is recruited to the plasma membrane when its own PH domain binds to PtdIns(3,4,5)P 3 , leading to colocalization of these two proteins and phosphorylation of PKB by PDK-1 on Thr-308 (1), resulting in PKB activation. Downstream substrates of PKB include the antiapoptotic protein BAD and Forkhead (FH) transcription factors. In addition to PKB, PDK-1 has also been reported to phosphorylate many other kinases, including ribosomal p70 protein kinases, that are involved in the regulation of protein translation (2-5).At the cellular level, PDK-1 regulates key insulin effects such a...

show abstract

“…The 3-phosphoinositide-dependent protein kinase-1 (PDK1) [ID: T5-1105] phosphorylates and activates members of the protein kinase AGC family and plays a key role in receptor tyrosine kinase signaling. A splice variant of mouse PDK-1, mPDK-1 beta, is highly expressed in the testis (Dong et al, 2002). Type II transmembrane serine proteases 11E [ID: T5-1106] and matriptase-3 [ID: T5-1107], an epithelial derived integral membrane serine protease whose expression is associated with breast, colon, prostate, and ovarian tumors, are both expressed in the testis (Hobson et al, 2004;Szabo et al, 2005).…”

Section: Testis-expressed Genes From Marginally Characterized or Unchmentioning

confidence: 99%

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 5: Intercellular junctions and contacts between germs cells and Sertoli cells and their regulatory interactions, testicular cholesterol, and genes/proteins associated with more than one germ cell generation

Hermo

Pelletier

Cyr

et al. 2009

Microscopy Res & Technique

View full text Add to dashboard Cite

In the testis, cell adhesion and junctional molecules permit specific interactions and intracellular communication between germ and Sertoli cells and apposed Sertoli cells. Among the many adhesion family of proteins, NCAM, nectin and nectin-like, catenins, and cadherens will be discussed, along with gap junctions between germ and Sertoli cells and the many members of the connexin family. The blood-testis barrier separates the haploid spermatids from blood borne elements. In the barrier, the intercellular junctions consist of many proteins such as occludin, tricellulin, and claudins. Changes in the expression of cell adhesion molecules are also an essential part of the mechanism that allows germ cells to move from the basal compartment of the seminiferous tubule to the adluminal compartment thus crossing the blood-testis barrier and well-defined proteins have been shown to assist in this process. Several structural components show interactions between germ cells to Sertoli cells such as the ectoplasmic specialization which are more closely related to Sertoli cells and tubulobulbar complexes that are processes of elongating spermatids embedded into Sertoli cells. Germ cells also modify several Sertoli functions and this also appears to be the case for residual bodies. Cholesterol plays a significant role during spermatogenesis and is essential for germ cell development. Lastly, we list genes/proteins that are expressed not only in any one specific generation of germ cells but across more than one generation.

show abstract

Cloning and characterization of a testis and brain-specific isoform of mouse 3′-phosphoinositide-dependent protein kinase-1, mPDK-1β

Cited by 11 publications

References 29 publications

piRNA profiling during specific stages of mouse spermatogenesis

piRNA profiling during specific stages of mouse spermatogenesis

Nuclear translocation of 3′-phosphoinositide-dependent protein kinase 1 (PDK-1): A potential regulatory mechanism for PDK-1 function

Contact Info

Product

Resources

About