Domain structure and sequence distribution in dentin phosphophoryn

Sabsay, Boris; Stetler-Stevenson, William G.; Lechner, Joseph H.; Veis, Arthur

doi:10.1042/bj2760699

Cited by 52 publications

(33 citation statements)

References 26 publications

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“…As noted by the underlines, there are five [SD] repeat sequences, [SD] m with m ϭ 2 or 3. These data are in agreement with the conclusions of Sabsay et al (11), who examined peptides released by enzymatic digestion and partial acid hydrolysis of intact phosphorylated PP. They had concluded that the end regions had to contain sequences containing the majority of the non-Ser and -Asp residues and flanked a central core composed almost completely of Ser and Asp(Asn).…”

Section: Resultssupporting

confidence: 82%

The Carboxyl-terminal Domain of Phosphophoryn Contains Unique Extended Triplet Amino Acid Repeat Sequences Forming Ordered Carboxyl-Phosphate Interaction Ridges That May Be Essential in the Biomineralization Process

George¹,

Bannon²,

Sabsay³

et al. 1996

Journal of Biological Chemistry

187

180

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Phosphophoryns (PPs), a family of Asp and Ser(P)-rich dentin proteins, are considered to be archetypal regulators of several aspects of extracellular matrix (ECM) biomineralization. We have cloned a rat incisor PP gene, Dmp2, from our odontoblast cDNA library and localized it to mouse chromosome 5q21 within 2 centimorgans of Dmp1, another tooth-specific ECM protein. The phosphophoryns (PPs) 1 (1) are a family of highly phosphorylated proteins with a unique composition and amino acid sequence. Found as the major noncollagenous proteins of the mineralized dentin matrix, the PPs have been considered to be the archetype of macromolecules that might regulate biomineralization processes (2, 3) by binding to the matrix of structural proteins (4), nucleating mineralization (5, 6), and controlling crystal growth (7). To understand how the PPs might carry out these diverse functions, it is crucial to know their amino acid sequences and structures. The PP from various species contain from 35 to 45 residue % aspartic acid and 40 to 55 residue % serine, of which as many as 90% of the Ser residues are phosphorylated (8, 9). The difficulties of Edman sequencing of phosphoserine-rich proteins have limited the information attainable by conventional sequencing efforts (10 -12) to a few internal acidic domains and a short amino-terminal sequence. Recently, chemical sequencing using means to derivatize the phosphoserines has provided a longer NH 2 -terminal sequence (13). Sequencing via cloning of a PP cDNA has also been difficult. A putative PP cDNA was described (14) several years ago, but no sequence data have been reported. Nucleotide probes have generally been unsuccessful because of the high redundancy of the Ser codons (15). Antibody screening of cDNA libraries was not fruitful because of the difficulties of producing high titer PP antibodies (16, 17).We have recently taken a new approach to the production of an antibody to a highly purified, dephosphorylated phosphophoryn (dPP) and, as described below, have been successful in using that antibody to identify several cDNAs in our established rat incisor odontoblast cDNA library (15,18). Sequencing of the clones obtained thus far yielded the expected AspSer-rich composition but, more importantly, revealed both an unexpected, unique "triplet cassette" repeat motif as well as a "doublet" repeat motif. These might account for several of the biomineralization regulatory functions of the phosphophoryns. We report here the nature of these unique sequence blocks. Furthermore, the identification of a PP cDNA clone has allowed the chromosomal localization of the corresponding PP gene. As shown below, the PP gene is colocalized with the gene for a mineralization disorder, dentinogenesis imperfecta, type II, correcting an erroneous assignment (14). EXPERIMENTAL PROCEDURESPP and Antibody Preparation-PP was extracted from rat incisors by the procedure of Rahima and Veis (9). The high M r PP components were isolated by CaCl 2 precipitation from the crude extract, followed by chromatography ...

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Section: Resultssupporting

confidence: 82%

The Carboxyl-terminal Domain of Phosphophoryn Contains Unique Extended Triplet Amino Acid Repeat Sequences Forming Ordered Carboxyl-Phosphate Interaction Ridges That May Be Essential in the Biomineralization Process

George¹,

Bannon²,

Sabsay³

et al. 1996

Journal of Biological Chemistry

187

180

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“…9 The NCPs of dentin, even though present in small quantities relative to collagen, are of significant functional importance in the mineralization process. [10][11][12] Dentin matrix protein1 (DMP1), dentin sialoprotein (DSP) and dentin phosphophoryn (DPP) are three NCPs that might play a regulatory role in dentin mineralization. 13 DMP1 was the first gene to be cloned from the mineralizing dentin matrix.…”

Section: Introductionmentioning

confidence: 99%

Dentin matrix protein 1 induces cytodifferentiation of dental pulp stem cells into odontoblasts

et al. 2005

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Odontoblasts are postmitotic cells that differentiate from the dental papilla. These cells are responsible for producing the calcified dentin matrix. The pulp-odontoblast interphase contains undifferentiated mesenchymal stem cells, which have the ability to cytodifferentiate into odontoblast-like cells in response to specific signaling molecules. Dentin matrix protein 1 (DMP1) is one of the dentin noncollagenous extracellular matrix proteins that has been implicated in regulation of mineralization. In this study, we have examined the potential role of DMP1 in inducing cytodifferentiation of dental pulp stem cells into odontoblast-like cells and formation of reparative dentin in a rat model. Cavities were drilled and pulps exposed in maxillary first molars. Collagen matrix impregnated with recombinant DMP1 was implanted directly in Group 1, while calcium hydroxide, a commonly used pulp-capping agent was implanted in group 2, collagen matrix that was not impregnated with rDMP1 was implanted directly in group 3, which served as control. Each of these three groups was subdivided into two subgroups, A for 2 weeks time duration and B for 4 weeks duration. At the end of the time period the maxillae were excised, tissues were processed for histological and immunohistochemical evaluations. The results showed that DMP1 could act as a morphogen on undifferentiated mesenchymal cells present in the dentin-pulp complex. These differentiated cells had the potential to regenerate dentin-like tissue, which was confirmed by the presence of collagenous matrix, odontoblast specific markers and calcified deposits. Gene Therapy (2006) 13, 611-620.

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“…Sequence analysis has been particularly difficult because of the lability of the PP during preparation and storage, and because of the overwhelming content of Ser and Asp. However, it became clear that the molecule was organized into domains which had to contain regions of (DS)N' (D)M, and (S)R, as well as a few regions richer in the other amino acids (Sabsay et al, 1991). Partial acid hydrolysis yielded sequences such as DD*D*DDDDDD*-and D***DD*, in which the * probably represented phosphoserine.…”

Section: (C) Other Bone Ncpsmentioning

confidence: 99%

Phosphorylation of the Proteins of the Extracellular Matrix of Mineralized Tissues By Casein Kinase-Like Activity

Veis

Sfeir

1997

Critical Reviews in Oral Biology & Medicine

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The extracellular matrix of the connective tissue contains non-collagenous proteins (NCP) which are acidic in character. The NCP of mineralizing systems (bone, dentin) differ from those of the non-mineralizing systems (skin, tendon) in that the mineralized tissue NCP are frequently phosphorylated. The phosphorylated proteins have been implicated in various aspects of the mineralization process. Thus, it is of interest to consider the mechanism and regulation of phosphorylation of the major matrix NCP. The majority of the phosphorylation takes place at Ser or Thr residues embedded within acidic sequences, and therefore are targets for casein kinase I (CKI ) or casein kinase 11 (CK2)-like kinases. CKI and CK2 are distantly related members of the protein kinase family. They are ubiquitous, constitutively active, second-messenger-independent kinases. CKI is found in a variety of isoforms, all homologous to the cx-subunit of the protein kinase family. It acts as a monomer. The active form of CK2 is a tetrameric holoenzyme, with 2 cx catalytic subunits and 2 ( regulatory subunits. The CK2 ac has activity alone, but the holoenzyme is four-to five-fold that activity. CK2 can use either ATP or GTP as the phosphate donor, but CK 1 can use only ATP. The CK2 activity which phosphorylates the mineralized tissue NCP appears to be localized to membraneassociated cell fractions, and is present in the endoplasmic reticulum and Golgi compartments in osteoblasts, where phosphorylation of the secreted proteins appears to take place as co-and post-translational processes. Data Bone and dentin are tissues in which mineral deposits of carbonate apatite form in an orderly fashion within a pre-formed collagen fibril matrix. Structural studies clearly show that the majority of the mineral phase is composed of carbonate-apatite crystals, whose crystal c-axes are aligned with the fibril axes of the collagen fibrils (FittonJackson, 1957;Glimcher and Krane, 1968;Glimcher, 1976;Weiner and Traub, 1986;Arsenault, 1988;Arsenault et al, 1991;Landis et al., 1992). Although much of the early work attempted to show that the collagen fibrils were responsible for the placement and induction of mineral deposition, this proposition was never verified. Instead, attention began to focus on the non-collagenous protein components of the matrix (Herring and Kent, 1963;Schlueter and Veis, 1964;Veis and Schlueter, 1964;Spector and Glimcher, 1972;Veis et al., 1972;Glimcher, 1976), especially since it was recognized that, as a class, the non-collagenous extracellular proteins (NCP) shared a common char360Crit Rev Oral Biol Med 8(4)

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Domain structure and sequence distribution in dentin phosphophoryn

Cited by 52 publications

References 26 publications

The Carboxyl-terminal Domain of Phosphophoryn Contains Unique Extended Triplet Amino Acid Repeat Sequences Forming Ordered Carboxyl-Phosphate Interaction Ridges That May Be Essential in the Biomineralization Process

The Carboxyl-terminal Domain of Phosphophoryn Contains Unique Extended Triplet Amino Acid Repeat Sequences Forming Ordered Carboxyl-Phosphate Interaction Ridges That May Be Essential in the Biomineralization Process

Dentin matrix protein 1 induces cytodifferentiation of dental pulp stem cells into odontoblasts

Phosphorylation of the Proteins of the Extracellular Matrix of Mineralized Tissues By Casein Kinase-Like Activity

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