Protobios LCC

Tallinn, Estonia

Protobios LCC

Tallinn, Estonia
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Maloverjan A.,Protobios LCC | Piirsoo M.,Tallinn University of Technology
Vitamins and Hormones | Year: 2012

Sonic Hedgehog (Shh) signaling pathway is implicated in various developmental and postnatal processes. Much of the current knowledge about the mechanisms of Shh signal transduction in vertebrates comes from the investigations of the respective pathway in fruit fly Drosophila melanogaster. In Drosophila, serine/threonine kinase fused is involved in all aspects of regulation of the Hh-dependent transcription factor cubitus interruptus possessing both catalytic and regulatory functions. Two proteins, Stk36 and Ulk3, share similarity with fu and have been suggested as mammalian fu homologues. However, in vivo data clarify that Stk36 is not required for embryonic development in mice and participates in Shh-independent genesis of motile cilia. Even if Stk36 is associated with any pathological or physiological aspect of postnatal Shh signaling in mammals, it has perhaps only regulatory functions since its catalytic activity seems to be lost during evolution. In contrast to Stk36, Ulk3 is an active kinase. In non-stimulated cells, Ulk3 catalytic activity is blocked, and it is involved in negative control of Gli proteins, mediators of Shh signaling. In response to Shh, Ulk3 positively regulates Gli proteins by directly phosphorylating them. Thus, Ulk3 is able to recapitulate both positive and negative roles of fu in vitro. However, Ulk3 functioning in vivo remains to be investigated. © 2012 Elsevier Inc.


Kauts M.-L.,Protobios LCC | Pihelgas S.,Protobios LCC | Orro K.,Protobios LCC | Neuman T.,Protobios LCC | And 2 more authors.
Stem Cell Research | Year: 2013

Several potential clinical applications of stem cells rely on their capacity to migrate into sites of inflammation where they contribute to tissue regeneration processes. Inflammatory signals are partially mediated by chemokines acting via their receptors expressed on the target cells. Data concerning the repertoire and biological activities of chemokine receptors in human adipose tissue derived stromal cells (ADSCs) are limited. Here we show that CCR1 is one of the few chemokine receptors expressed in ADSCs at a high level. CCR1 expression varies in ADSCs derived from different donors. It sharply decreases in the early phase of ADSCs in vitro propagation, but further demonstrates relative stability. Expression of CCR1 positively correlates with expression of SOX2, OCT4 and NANOG, transcription factors responsible for maintenance of the stemness properties of the cells. We demonstrate that signaling via CCL5/CCR1 axis triggers migration of ADSCs, activates ERK and AKT kinases, stimulates NFκB transcriptional activity and culminates in increased proliferation of CCR1+ cells accompanied with up-regulation of SOX2, OCT4 and NANOG expression. Our data suggest that chemokine signaling via CCR1 may be involved in regulation of stemness of ADSCs. © 2012 Elsevier B.V.


PubMed | Protobios LCC
Type: | Journal: Vitamins and hormones | Year: 2012

Sonic Hedgehog (Shh) signaling pathway is implicated in various developmental and postnatal processes. Much of the current knowledge about the mechanisms of Shh signal transduction in vertebrates comes from the investigations of the respective pathway in fruit fly Drosophila melanogaster. In Drosophila, serine/threonine kinase fused is involved in all aspects of regulation of the Hh-dependent transcription factor cubitus interruptus possessing both catalytic and regulatory functions. Two proteins, Stk36 and Ulk3, share similarity with fu and have been suggested as mammalian fu homologues. However, in vivo data clarify that Stk36 is not required for embryonic development in mice and participates in Shh-independent genesis of motile cilia. Even if Stk36 is associated with any pathological or physiological aspect of postnatal Shh signaling in mammals, it has perhaps only regulatory functions since its catalytic activity seems to be lost during evolution. In contrast to Stk36, Ulk3 is an active kinase. In non-stimulated cells, Ulk3 catalytic activity is blocked, and it is involved in negative control of Gli proteins, mediators of Shh signaling. In response to Shh, Ulk3 positively regulates Gli proteins by directly phosphorylating them. Thus, Ulk3 is able to recapitulate both positive and negative roles of fu in vitro. However, Ulk3 functioning in vivo remains to be investigated.

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