The Experts below are selected from a list of 156 Experts worldwide ranked by ideXlab platform
Larry W. Fisher - One of the best experts on this subject based on the ideXlab platform.
-
DMP1 and DSPP: Evidence for Duplication and Convergent Evolution of Two SIBLING Proteins
Cells tissues organs, 2011Co-Authors: Larry W. FisherAbstract:Since first being proposed as a tandem gene family in 2001, the relatedness of the 5 SIBLING Proteins (BSP, DMP1, DSPP, MEPE, and SPP1/OPN) has predominantly depended on arguments involving shared intron/exon properties as well as conserved protein biochemical properties (e.g. unstructured and acidic) and specific peptide motifs (e.g. phosphorylation and integrin-binding RGD). This report discusses the evidence that an ancient DMP1 gene underwent a simple duplication in the common ancestor of mammals and reptiles and then separately evolved into DSPP-like paralogs in the 2 classes. Genomic sequence analyses show that different copies of the original DMP1 duplication process were selected by mammalian and reptilian (anole lizard) classes to acquire genetically different but biochemically similar phosphoserine-rich repeat domains by convergent evolution. Mammals, for example, expanded phosphoserine motifs encoded exclusively using motifs containing AGC/T serine codons while the reptile line's repeats also used TCN-encoding serine codons. A similar analysis of the origins of the other 4 SIBLINGs will require even more detailed analysis as genome sequences of various fish and amphibia become available.
-
Dentin sialophosphoprotein (DSPP) is cleaved into its two natural dentin matrix products by three isoforms of bone morphogenetic protein-1 (BMP1).
Matrix biology : journal of the International Society for Matrix Biology, 2010Co-Authors: Zofia Von Marschall, Larry W. FisherAbstract:The protease that cleaves the most abundant non-collagenous protein of dentin matrix, dentin sialophosphoprotein (DSPP), into its two final dentin matrix products, dentin sialoprotein (DSP) and dentin phosphoprotein (DPP), has not been directly identified. In this study, full-length recombinant mouse DSPP was made for the first time in furin-deficient mammalian LoVo cells and used to test the ability of three different isoforms of one candidate protease, bone morphogenetic protein-1 (BMP1) to cleave DSPP at the appropriate site. Furthermore, two reported enhancers of BMP1/mTLD activity (procollagen C-endopeptidase enhancer-1, PCPE-1, and secreted frizzled-related protein-2, sFRP2) were tested for their abilities to modulate BMP1-mediated processing of both DSPP and another SIBLING family member with a similar cleavage motif, dentin matrix protein-1 (DMP1). Three splice variants of BMP1 (classic BMP1, the full-length mTolloid (mTLD), and the shorter isoform lacking the CUB3 domain, BMP1-5) were all shown to cleave the recombinant DSPP in vitro although mTLD was relatively inefficient at processing both DSPP and DMP1. Mutation of the MQGDD peptide motif to IEGDD completely eliminated the ability of all three recombinant isoforms to process full-length recombinant DSPP in vitro thereby verifying the single predicted cleavage site. Furthermore when human bone marrow stromal cells (which naturally express furin-activated BMP1) were transduced with the adenovirus-encoding either wild-type or mutant DSPP, they were observed to fully cleave wild-type DSPP but failed to process the mutant DSPP(MQDeltaIE) during biogenesis. All three BMP1 isoforms were shown to process type I procollagen as well as DSPP and DMP1 much more efficiently in low-salt buffer (< or = 50 mM NaCl) compared to commonly used normal saline buffers (150 mM NaCl). Neither PCPE-1 nor sFRP2 were able to enhance any of the three BMP1 isoforms in cleaving either DSPP or DMP1 under either low or normal saline conditions. Interestingly, we were unable to reproduce sFRP2's reported ability to enhance the processing of type I procollagen by BMP1/mTLD. In summary, three isoforms of BMP1 process both DSPP and DMP1 at the MQX/DDP motif, but the identity of a protein that can enhance the cleavage of the two SIBLING Proteins remains elusive.
-
up regulation of SIBLING Proteins and correlation with cognate mmp expression in oral cancer
Oral Oncology, 2007Co-Authors: Kalu U E Ogbureke, Nikolaos G. Nikitakis, Gary Warburton, Robert A. Ord, John J. Sauk, Jennifer L. Waller, Larry W. FisherAbstract:Various combinations of the SIBLING family of Proteins have been found to be up-regulated in many human cancers and have been linked to different stages of tumor progression, including metastasis. Bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1) specifically bind and activate MMP-2, MMP-3, and MMP-9, respectively. These proteases have also been shown to play important roles in oral squamous cell carcinoma (OSCC) invasion and metastasis. However, with the exception of OPN, there are no reports on the expression of the family of five SIBLING Proteins in OSCC. This study examines the expression patterns of the SIBLING family (and MMP partners when known) in OSCC, correlating expression to outcome variables. Archived paraffin sections of 87 cases of primary OSCC were screened by immunohistochemistry for the SIBLINGs and their MMP partners. Three SIBLINGs (BSP, DSPP, and OPN), were expressed in OSCC, while DMP1 and MEPE expression were never observed. Furthermore, BSP and OPN were always expressed with their known MMP partners, MMP-2 and MMP-3, respectively. Poorly differentiated tumors exhibited reduced or no immunoreactivity for BSP and OPN but increased immunoreactivity for DSPP. Seventy eight (90%) cases were positive for BSP and DSPP, while 79 cases (91%) were positive for OPN. Overall, 91% of the cases were positive for at least one SIBLING. There were no correlations between SIBLING expression and tumor size ("T"; of the Union Internationale Contre le Cancer [UICC]-TNM classification for OSCC), and between SIBLING expression and lymph node spread for the T1/T2 tumors. The levels of DSPP expression for floor of mouth and retromolar region tumors were higher than for tongue tumors. Statistically significant correlations were, however, found between the expression levels of BSP and MMP-2 (p<0.0001), BSP and MMP-3 (p<0.0001), and OPN and MMP-3 (p<0.0024). We conclude that BSP, DSPP, and OPN are highly up-regulated in OSCC. While the production of these SIBLINGs is independent of T, they correlate with oral location of tumor, cognate MMP expression, and for DSPP, the degree of tumor differentiation.
-
Up-regulation of SIBLING Proteins and correlation with cognate MMP expression in oral cancer
Oral oncology, 2007Co-Authors: Kalu U E Ogbureke, Nikolaos G. Nikitakis, Gary Warburton, Robert A. Ord, John J. Sauk, Jennifer L. Waller, Larry W. FisherAbstract:Various combinations of the SIBLING family of Proteins have been found to be up-regulated in many human cancers and have been linked to different stages of tumor progression, including metastasis. Bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1) specifically bind and activate MMP-2, MMP-3, and MMP-9, respectively. These proteases have also been shown to play important roles in oral squamous cell carcinoma (OSCC) invasion and metastasis. However, with the exception of OPN, there are no reports on the expression of the family of five SIBLING Proteins in OSCC. This study examines the expression patterns of the SIBLING family (and MMP partners when known) in OSCC, correlating expression to outcome variables. Archived paraffin sections of 87 cases of primary OSCC were screened by immunohistochemistry for the SIBLINGs and their MMP partners. Three SIBLINGs (BSP, DSPP, and OPN), were expressed in OSCC, while DMP1 and MEPE expression were never observed. Furthermore, BSP and OPN were always expressed with their known MMP partners, MMP-2 and MMP-3, respectively. Poorly differentiated tumors exhibited reduced or no immunoreactivity for BSP and OPN but increased immunoreactivity for DSPP. Seventy eight (90%) cases were positive for BSP and DSPP, while 79 cases (91%) were positive for OPN. Overall, 91% of the cases were positive for at least one SIBLING. There were no correlations between SIBLING expression and tumor size ("T"; of the Union Internationale Contre le Cancer [UICC]-TNM classification for OSCC), and between SIBLING expression and lymph node spread for the T1/T2 tumors. The levels of DSPP expression for floor of mouth and retromolar region tumors were higher than for tongue tumors. Statistically significant correlations were, however, found between the expression levels of BSP and MMP-2 (p
-
renal expression of SIBLING Proteins and their partner matrix metalloproteinases mmps
Kidney International, 2005Co-Authors: Kalu U E Ogbureke, Larry W. FisherAbstract:Renal expression of SIBLING Proteins and their partner matrix metalloproteinases (MMP). Background Three members of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of Proteins have recently been shown to bind and activate specific promatrix metalloproteinases (MMPs) and to overcome the inhibition of tissue inhibitors of MMPs (TIMPs). Although usually associated with mineralized tissues, we have shown that the SIBLINGs and their MMP partners, when known, are coexpressed in salivary gland ductal cells. The present study examined the expression patterns of both the SIBLINGs and their MMP partners in adult kidney. Methods The expression patterns of all five SIBLINGs known to date, and their MMP partners were determined in monkey kidney using immunohistochemistry and in situ hybridization techniques. Results Bone sialoprotein (BSP) and its partner, MMP-2, were coexpressed in both the proximal and distal tubules. Osteopontin, as previously shown, was expressed in the distal tubules while its partner MMP-3 was expressed in both the proximal tubule and distal tubles. Dentin matrix protein-1 (DMP1) and MMP-9 were coexpressed throughout the nephron, including both parietal cells of Bowman's capsule and the thin limb of the loop of Henle. Dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE) were expressed in the proximal tubule and distal tubule, and proximal tubule, respectively. Conclusion In contrast to salivary gland in which all SIBLINGs and their MMP partners were coexpressed throughout the length of the ducts, these Proteins were differentially expressed within the normal adult nephron. We hypothesize that the cells use the SIBLING/MMP pairs in the normal turnover of cell surface Proteins and/or pericellular matrix Proteins such as those in basement membranes.
Kalu U E Ogbureke - One of the best experts on this subject based on the ideXlab platform.
-
up regulation of SIBLING Proteins and correlation with cognate mmp expression in oral cancer
Oral Oncology, 2007Co-Authors: Kalu U E Ogbureke, Nikolaos G. Nikitakis, Gary Warburton, Robert A. Ord, John J. Sauk, Jennifer L. Waller, Larry W. FisherAbstract:Various combinations of the SIBLING family of Proteins have been found to be up-regulated in many human cancers and have been linked to different stages of tumor progression, including metastasis. Bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1) specifically bind and activate MMP-2, MMP-3, and MMP-9, respectively. These proteases have also been shown to play important roles in oral squamous cell carcinoma (OSCC) invasion and metastasis. However, with the exception of OPN, there are no reports on the expression of the family of five SIBLING Proteins in OSCC. This study examines the expression patterns of the SIBLING family (and MMP partners when known) in OSCC, correlating expression to outcome variables. Archived paraffin sections of 87 cases of primary OSCC were screened by immunohistochemistry for the SIBLINGs and their MMP partners. Three SIBLINGs (BSP, DSPP, and OPN), were expressed in OSCC, while DMP1 and MEPE expression were never observed. Furthermore, BSP and OPN were always expressed with their known MMP partners, MMP-2 and MMP-3, respectively. Poorly differentiated tumors exhibited reduced or no immunoreactivity for BSP and OPN but increased immunoreactivity for DSPP. Seventy eight (90%) cases were positive for BSP and DSPP, while 79 cases (91%) were positive for OPN. Overall, 91% of the cases were positive for at least one SIBLING. There were no correlations between SIBLING expression and tumor size ("T"; of the Union Internationale Contre le Cancer [UICC]-TNM classification for OSCC), and between SIBLING expression and lymph node spread for the T1/T2 tumors. The levels of DSPP expression for floor of mouth and retromolar region tumors were higher than for tongue tumors. Statistically significant correlations were, however, found between the expression levels of BSP and MMP-2 (p<0.0001), BSP and MMP-3 (p<0.0001), and OPN and MMP-3 (p<0.0024). We conclude that BSP, DSPP, and OPN are highly up-regulated in OSCC. While the production of these SIBLINGs is independent of T, they correlate with oral location of tumor, cognate MMP expression, and for DSPP, the degree of tumor differentiation.
-
Up-regulation of SIBLING Proteins and correlation with cognate MMP expression in oral cancer
Oral oncology, 2007Co-Authors: Kalu U E Ogbureke, Nikolaos G. Nikitakis, Gary Warburton, Robert A. Ord, John J. Sauk, Jennifer L. Waller, Larry W. FisherAbstract:Various combinations of the SIBLING family of Proteins have been found to be up-regulated in many human cancers and have been linked to different stages of tumor progression, including metastasis. Bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1) specifically bind and activate MMP-2, MMP-3, and MMP-9, respectively. These proteases have also been shown to play important roles in oral squamous cell carcinoma (OSCC) invasion and metastasis. However, with the exception of OPN, there are no reports on the expression of the family of five SIBLING Proteins in OSCC. This study examines the expression patterns of the SIBLING family (and MMP partners when known) in OSCC, correlating expression to outcome variables. Archived paraffin sections of 87 cases of primary OSCC were screened by immunohistochemistry for the SIBLINGs and their MMP partners. Three SIBLINGs (BSP, DSPP, and OPN), were expressed in OSCC, while DMP1 and MEPE expression were never observed. Furthermore, BSP and OPN were always expressed with their known MMP partners, MMP-2 and MMP-3, respectively. Poorly differentiated tumors exhibited reduced or no immunoreactivity for BSP and OPN but increased immunoreactivity for DSPP. Seventy eight (90%) cases were positive for BSP and DSPP, while 79 cases (91%) were positive for OPN. Overall, 91% of the cases were positive for at least one SIBLING. There were no correlations between SIBLING expression and tumor size ("T"; of the Union Internationale Contre le Cancer [UICC]-TNM classification for OSCC), and between SIBLING expression and lymph node spread for the T1/T2 tumors. The levels of DSPP expression for floor of mouth and retromolar region tumors were higher than for tongue tumors. Statistically significant correlations were, however, found between the expression levels of BSP and MMP-2 (p
-
renal expression of SIBLING Proteins and their partner matrix metalloproteinases mmps
Kidney International, 2005Co-Authors: Kalu U E Ogbureke, Larry W. FisherAbstract:Renal expression of SIBLING Proteins and their partner matrix metalloproteinases (MMP). Background Three members of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of Proteins have recently been shown to bind and activate specific promatrix metalloproteinases (MMPs) and to overcome the inhibition of tissue inhibitors of MMPs (TIMPs). Although usually associated with mineralized tissues, we have shown that the SIBLINGs and their MMP partners, when known, are coexpressed in salivary gland ductal cells. The present study examined the expression patterns of both the SIBLINGs and their MMP partners in adult kidney. Methods The expression patterns of all five SIBLINGs known to date, and their MMP partners were determined in monkey kidney using immunohistochemistry and in situ hybridization techniques. Results Bone sialoprotein (BSP) and its partner, MMP-2, were coexpressed in both the proximal and distal tubules. Osteopontin, as previously shown, was expressed in the distal tubules while its partner MMP-3 was expressed in both the proximal tubule and distal tubles. Dentin matrix protein-1 (DMP1) and MMP-9 were coexpressed throughout the nephron, including both parietal cells of Bowman's capsule and the thin limb of the loop of Henle. Dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE) were expressed in the proximal tubule and distal tubule, and proximal tubule, respectively. Conclusion In contrast to salivary gland in which all SIBLINGs and their MMP partners were coexpressed throughout the length of the ducts, these Proteins were differentially expressed within the normal adult nephron. We hypothesize that the cells use the SIBLING/MMP pairs in the normal turnover of cell surface Proteins and/or pericellular matrix Proteins such as those in basement membranes.
-
Renal expression of SIBLING Proteins and their partner matrix metalloproteinases (MMPs)
Kidney international, 2005Co-Authors: Kalu U E Ogbureke, Larry W. FisherAbstract:Three members of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of Proteins have recently been shown to bind and activate specific promatrix metalloproteinases (MMPs) and to overcome the inhibition of tissue inhibitors of MMPs (TIMPs). Although usually associated with mineralized tissues, we have shown that the SIBLINGs and their MMP partners, when known, are coexpressed in salivary gland ductal cells. The present study examined the expression patterns of both the SIBLINGs and their MMP partners in adult kidney. The expression patterns of all five SIBLINGs known to date, and their MMP partners were determined in monkey kidney using immunohistochemistry and in situ hybridization techniques. Bone sialoprotein (BSP) and its partner, MMP-2, were coexpressed in both the proximal and distal tubules. Osteopontin, as previously shown, was expressed in the distal tubules while its partner MMP-3 was expressed in both the proximal tubule and distal tubles. Dentin matrix protein-1 (DMP1) and MMP-9 were coexpressed throughout the nephron, including both parietal cells of Bowman's capsule and the thin limb of the loop of Henle. Dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE) were expressed in the proximal tubule and distal tubule, and proximal tubule, respectively. In contrast to salivary gland in which all SIBLINGs and their MMP partners were coexpressed throughout the length of the ducts, these Proteins were differentially expressed within the normal adult nephron. We hypothesize that the cells use the SIBLING/MMP pairs in the normal turnover of cell surface Proteins and/or pericellular matrix Proteins such as those in basement membranes.
-
Expression of SIBLINGs and Their Partner MMPs in Salivary Glands
Journal of dental research, 2004Co-Authors: Kalu U E Ogbureke, Larry W. FisherAbstract:Three members of the SIBLING family of integrin-binding phosphoglycoProteins (bone sialoprotein, BSP; osteopontin, OPN; and dentin matrix protein-1, DMP1) were recently shown to bind with high affinity (nM) and to activate 3 different matrix metalloproteinases (MMP-2, MMP-3, and MMP-9, respectively) in vitro. The current study was designed to document the possible biological relevance of the SIBLING-MMP activation pathway in vivo by showing that these 3 SIBLINGs and their known MMP partners are co-expressed in normal adult tissue. BSP, OPN, and DMP1 were invariably co-expressed with their partner MMPs in salivary glands of humans and mice. The 2 SIBLING Proteins without known MMP partners, dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE), were also expressed in salivary glands. Expression of all SIBLINGs in this normal, non-mineralizing epithelial tissue suggests that they serve at least one function in vivo other than directly promoting matrix mineralization--a function we hypothesize involves local activation of MMPs.
Chunlin Qin - One of the best experts on this subject based on the ideXlab platform.
-
Adhesion of MC3T3‐E1 cells bound to dentin phosphoprotein specifically bound to collagen type I
Journal of biomedical materials research. Part A, 2012Co-Authors: Kevin M. Zurick, Chunlin Qin, Matthew T. BernardsAbstract:Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (small integrin binding N-linked glycoprotein) family of Proteins commonly found in mineralized tissues. Dentin phosphoprotein (DPP) is a naturally occurring subdomain of DSPP that contains the cell binding RGD sequence. Previously, the orientation and conformation of other SIBLING family members specifically bound to collagen I have been investigated with respect to their cell adhesion properties. In this study, the orientation of DPP under similar circumstances is examined, and the results are discussed relative to the previous investigations. Radiolabeled adsorption isotherms were developed for DPP adsorbing to both tissue culture polystyrene (TCPS) and collagen coated TCPS. Then, a MC3T3-E1 cell adhesion assay was performed on TCPS and collagen coated TCPS in the presence of identical amounts of adsorbed DPP. It was discovered that there was a significant difference in the number of bound cells on the TCPS and collagen coated TCPS, with a preference for TCPS. Furthermore, a cell inhibition assay was conducted to confirm that the cell binding that occurred was due to specific integrin interactions with the RGD sequence of DPP. These results suggest that the orientation of DPP, rather than its conformation, dictates the accessibility of the cell binding RGD domains of DPP and that the RGD sequence in DPP is less accessible when DPP is specifically bound to collagen. The results obtained in this study are in stark contrast to previous studies with related SIBLING Proteins, and suggest that DPP does not play a key role in cell binding to the collagen matrix of developing bone.
-
expression and distribution of SIBLING Proteins in the predentin dentin and mandible of hyp mice
Oral Diseases, 2010Co-Authors: B Zhang, Yao Sun, L Chen, C Guan, L Guo, Chunlin QinAbstract:Oral Diseases (2010) 16, 453–464 Objectives: Human X-linked hypophosphatemia (XLH) and its murine homologue, Hyp are caused by inactivating mutations in PHEX gene. The protein encoded by PHEX gene is an endopeptidase whose physiological substrate(s) has not been identified. Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP), two members of the Small Integrin-Binding LIgand, N-linked Glycoprotein (SIBLING) family are proteolytically processed. It has been speculated that PHEX endopeptidase may be responsible for the proteolytic cleavage of DMP1 and DSPP. To test this hypothesis and to analyse the distribution of SIBLING Proteins in the predentin/dentin complex and mandible of Hyp mice, we compared the expression of four SIBLING Proteins, DMP1, DSPP, bone sialoprotein (BSP) and osteopontin (OPN) between Hyp and wild-type mice. Methods: These SIBLING Proteins were analysed by protein chemistry and immunohistochemistry. Results: (1) Dentin matrix protein 1 and DSPP fragments are present in the extracts of Hyp predentin/dentin and bone; (2) the level of DMP1 proteoglycan form, BSP and OPN is elevated in the Hyp bone. Conclusions: The PHEX protein is not the enzyme responsible for the proteolytic processing of DMP1 and DSPP. The altered distribution of SIBLING Proteins may be involved in the pathogenesis of bone and dentin defects in Hyp and XLH.
-
Expression and distribution of SIBLING Proteins in the predentin/dentin and mandible of hyp mice
Oral diseases, 2010Co-Authors: B Zhang, Yao Sun, L Chen, C Guan, L Guo, Chunlin QinAbstract:Oral Diseases (2010) 16, 453–464 Objectives: Human X-linked hypophosphatemia (XLH) and its murine homologue, Hyp are caused by inactivating mutations in PHEX gene. The protein encoded by PHEX gene is an endopeptidase whose physiological substrate(s) has not been identified. Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP), two members of the Small Integrin-Binding LIgand, N-linked Glycoprotein (SIBLING) family are proteolytically processed. It has been speculated that PHEX endopeptidase may be responsible for the proteolytic cleavage of DMP1 and DSPP. To test this hypothesis and to analyse the distribution of SIBLING Proteins in the predentin/dentin complex and mandible of Hyp mice, we compared the expression of four SIBLING Proteins, DMP1, DSPP, bone sialoprotein (BSP) and osteopontin (OPN) between Hyp and wild-type mice. Methods: These SIBLING Proteins were analysed by protein chemistry and immunohistochemistry. Results: (1) Dentin matrix protein 1 and DSPP fragments are present in the extracts of Hyp predentin/dentin and bone; (2) the level of DMP1 proteoglycan form, BSP and OPN is elevated in the Hyp bone. Conclusions: The PHEX protein is not the enzyme responsible for the proteolytic processing of DMP1 and DSPP. The altered distribution of SIBLING Proteins may be involved in the pathogenesis of bone and dentin defects in Hyp and XLH.
-
Distribution of Small Integrin-Binding LIgand, N-linked GlycoProteins (SIBLING) in the condylar cartilage of rat mandible
International journal of oral and maxillofacial surgery, 2010Co-Authors: Yao Sun, Vikram Gandhi, Monica Prasad, Xiaofang Wang, Qinglin Zhu, Jian Q. Feng, Robert J. Hinton, Chunlin QinAbstract:The Small Integrin-Binding LIgand, N-linked Glycoprotein (SIBLING) family is one category of non-collagenous Proteins closely related to osteogenesis. In this study, the authors systematically evaluated the presence and distribution of four SIBLING family members, dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), bone sialoprotein (BSP) and osteopontin (OPN), in rat mandibular condylar cartilage using protein chemistry and immunohistochemistry. For protein chemistry, SIBLING Proteins in the dissected condylar cartilage were extracted with 4M guanidium-HCl, separated by ion-exchange chromatography, and analyzed by Western immunoblotting. Immunohistochemistry was employed to assess the distribution of these four SIBLING Proteins in the condylar cartilage of 2-, 5- and 8-week-old rats. Results from both approaches showed that all four members are expressed in the condylar cartilage. DSPP, unlike that observed in dentin and bone, exists as a full-length form (uncleaved) in the condylar cartilage. The NH(2)-terminal fragment of DMP1 is mainly detected in the matrix of the cartilage while the COOH-terminal fragment is primarily localized in the nuclei of cells in the chondroblastic and hypertrophic layers. The data obtained in this investigation provide clues about the potential roles of these SIBLING Proteins in chondrogenesis.
-
Expression and processing of small integrin-binding ligand N-linked glycoProteins in mouse odontoblastic cells
Archives of oral biology, 2008Co-Authors: Shuo Chen, Chunlin Qin, Lei Chen, Allen Jahangiri, Bo Chen, Hui Hsiu Chuang, Mary MacdougallAbstract:Small integrin-binding ligand N-linked glycoProteins (SIBLINGs) are expressed in dentin and believed to control dentinogenesis. Five members of SIBLING family include bone sialoprotein (BSP), osteopontin (OPN), matrix extracellular phosphoglycoprotein (MEPE), dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP). These genes are clustered on chromosome 4q in humans and share similar biological features. DSPP and DMP1 are processed into given structural/functional fragments in rat and porcine. It still remains unclear whether these evidences occur in mouse and other SIBLING members are also processed into given fragments from their parent precursors. The aim of this study was to identify expression and processing of the five Proteins in two mouse odontoblastic cell lines. Two mouse odontoblastic cells were used to study expression and processing of the five SIBLING Proteins by immunohistochemistry and Western blot analyses. Immunohistochemistry study showed that all of the five SIBLING members were expressed within the cytoplasm and cellular processes in the mouse odontoblastic cell lines. Expression levels of DMP1 and DSPP were higher in differentiated mouse odontoblasts than undifferentiated mouse odontoblasts. Immunolabelling signal of DSP and MEPE was also detected within the nucleus in the two cell lines. Western blot assay indicated that all five members were processed into at least two fragments in these cells. These results suggest that different processed products and expression levels of the SIBLING Proteins may play distinct biological functions in tooth development and mineralisation.
Paul R Albert - One of the best experts on this subject based on the ideXlab platform.
-
rgs17 rgsz2 and the rz a family of regulators of g protein signaling
Seminars in Cell & Developmental Biology, 2006Co-Authors: Caroline Nunn, Peter Chidiac, Paul R AlbertAbstract:Abstract Regulators of G-protein signaling (RGS Proteins) comprise over 20 different Proteins that have been classified into subfamilies on the basis of structural homology. The RZ/A family includes RGSZ2/RGS17 (the most recently discovered member of this family), GAIP/RGS19, RGSZ1/RGS20, and the RGSZ1 variant Ret-RGS. The RGS Proteins are GTPase activating Proteins (GAPs) that turn off G-Proteins and thus negatively regulate the signaling of G-protein coupled receptors (GPCRs). In addition, some RZ/A family RGS Proteins are able to modify signaling through interactions with adapter Proteins (such as GIPC and GIPN). The RZ/A Proteins have a simple structure that includes a conserved amino-terminal cysteine string motif, RGS box and short carboxyl-terminal, which confer GAP activity (RGS box) and the ability to undergo covalent modification and interact with other Proteins (amino-terminal). This review focuses on RGS17 and its RZ/A SIBLING Proteins and discusses the similarities and differences among these Proteins in terms of their palmitoylation, phosphorylation, intracellular localization and interactions with GPCRs and adapter Proteins. The specificity of these RGS protein for different Gα Proteins and receptors, and the consequences for signaling are discussed. The tissue and brain distribution, and the evolving understanding of the roles of this family of RGS Proteins in receptor signaling and brain function are highlighted.
-
RGS17/RGSZ2 and the RZ/A family of regulators of G-protein signaling.
Seminars in Cell & Developmental Biology, 2006Co-Authors: Caroline Nunn, Peter Chidiac, Paul R AlbertAbstract:Abstract Regulators of G-protein signaling (RGS Proteins) comprise over 20 different Proteins that have been classified into subfamilies on the basis of structural homology. The RZ/A family includes RGSZ2/RGS17 (the most recently discovered member of this family), GAIP/RGS19, RGSZ1/RGS20, and the RGSZ1 variant Ret-RGS. The RGS Proteins are GTPase activating Proteins (GAPs) that turn off G-Proteins and thus negatively regulate the signaling of G-protein coupled receptors (GPCRs). In addition, some RZ/A family RGS Proteins are able to modify signaling through interactions with adapter Proteins (such as GIPC and GIPN). The RZ/A Proteins have a simple structure that includes a conserved amino-terminal cysteine string motif, RGS box and short carboxyl-terminal, which confer GAP activity (RGS box) and the ability to undergo covalent modification and interact with other Proteins (amino-terminal). This review focuses on RGS17 and its RZ/A SIBLING Proteins and discusses the similarities and differences among these Proteins in terms of their palmitoylation, phosphorylation, intracellular localization and interactions with GPCRs and adapter Proteins. The specificity of these RGS protein for different Gα Proteins and receptors, and the consequences for signaling are discussed. The tissue and brain distribution, and the evolving understanding of the roles of this family of RGS Proteins in receptor signaling and brain function are highlighted.
Caroline Nunn - One of the best experts on this subject based on the ideXlab platform.
-
rgs17 rgsz2 and the rz a family of regulators of g protein signaling
Seminars in Cell & Developmental Biology, 2006Co-Authors: Caroline Nunn, Peter Chidiac, Paul R AlbertAbstract:Abstract Regulators of G-protein signaling (RGS Proteins) comprise over 20 different Proteins that have been classified into subfamilies on the basis of structural homology. The RZ/A family includes RGSZ2/RGS17 (the most recently discovered member of this family), GAIP/RGS19, RGSZ1/RGS20, and the RGSZ1 variant Ret-RGS. The RGS Proteins are GTPase activating Proteins (GAPs) that turn off G-Proteins and thus negatively regulate the signaling of G-protein coupled receptors (GPCRs). In addition, some RZ/A family RGS Proteins are able to modify signaling through interactions with adapter Proteins (such as GIPC and GIPN). The RZ/A Proteins have a simple structure that includes a conserved amino-terminal cysteine string motif, RGS box and short carboxyl-terminal, which confer GAP activity (RGS box) and the ability to undergo covalent modification and interact with other Proteins (amino-terminal). This review focuses on RGS17 and its RZ/A SIBLING Proteins and discusses the similarities and differences among these Proteins in terms of their palmitoylation, phosphorylation, intracellular localization and interactions with GPCRs and adapter Proteins. The specificity of these RGS protein for different Gα Proteins and receptors, and the consequences for signaling are discussed. The tissue and brain distribution, and the evolving understanding of the roles of this family of RGS Proteins in receptor signaling and brain function are highlighted.
-
RGS17/RGSZ2 and the RZ/A family of regulators of G-protein signaling.
Seminars in Cell & Developmental Biology, 2006Co-Authors: Caroline Nunn, Peter Chidiac, Paul R AlbertAbstract:Abstract Regulators of G-protein signaling (RGS Proteins) comprise over 20 different Proteins that have been classified into subfamilies on the basis of structural homology. The RZ/A family includes RGSZ2/RGS17 (the most recently discovered member of this family), GAIP/RGS19, RGSZ1/RGS20, and the RGSZ1 variant Ret-RGS. The RGS Proteins are GTPase activating Proteins (GAPs) that turn off G-Proteins and thus negatively regulate the signaling of G-protein coupled receptors (GPCRs). In addition, some RZ/A family RGS Proteins are able to modify signaling through interactions with adapter Proteins (such as GIPC and GIPN). The RZ/A Proteins have a simple structure that includes a conserved amino-terminal cysteine string motif, RGS box and short carboxyl-terminal, which confer GAP activity (RGS box) and the ability to undergo covalent modification and interact with other Proteins (amino-terminal). This review focuses on RGS17 and its RZ/A SIBLING Proteins and discusses the similarities and differences among these Proteins in terms of their palmitoylation, phosphorylation, intracellular localization and interactions with GPCRs and adapter Proteins. The specificity of these RGS protein for different Gα Proteins and receptors, and the consequences for signaling are discussed. The tissue and brain distribution, and the evolving understanding of the roles of this family of RGS Proteins in receptor signaling and brain function are highlighted.