Mutations in collagen genes. Consequences for rare and common diseases.

Prockop, Darwin J.

doi:10.1172/jci111773

Cited by 40 publications

(10 citation statements)

References 26 publications

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“…At the cellular level, the best characterized defect in VLK null animals is in the differentiation of chondrocytes in long bones (Imuta et al, 2009; Kinoshita et al, 2009; Probst et al, 2013). Our studies identify a variety of VLK substrates with established roles in skeletal development, including Type I collagen (Prockop, 1985), MMP13 (Stickens et al, 2004), MIA3 (an essential collagen chaperone) (Wilson et al, 2011), and MESD (a chaperone for the wnt receptor LRP5/6) (Hsieh et al, 2003; Zhang et al, 2004). At this point, it is not possible to assess whether the VLK null phenotype reflects a major functional alteration in one or two key substrates, or more subtle changes in a broad set of functionally interacting substrates that collectively impact chondrocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

A Secreted Tyrosine Kinase Acts in the Extracellular Environment

Bordoli

Yum

Breitkopf

et al. 2014

Cell

113

118

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Summary Although tyrosine phosphorylation of extracellular proteins has been reported to occur extensively in vivo, no secreted protein tyrosine kinase has been identified. As a result, investigation of the potential role of extracellular tyrosine phosphorylation in physiological and pathological tissue regulation has not been possible. Here we show that VLK, a putative protein kinase previously shown to be essential in embryonic development, is a secreted protein kinase, with preference for tyrosine, that phosphorylates a broad range of secreted and ER-resident substrate proteins. We find that VLK is rapidly and quantitatively secreted from platelets in response to stimuli, and can tyrosine phosphorylate co-released proteins utilizing endogenous as well as exogenous ATP sources. We propose that discovery of VLK activity provides an explanation for the extensive and conserved pattern of extracellular tyrosine phosphophorylation seen in vivo, and extends the importance of regulated tyrosine phosphorylation into the extracellular environment.

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Section: Discussionmentioning

confidence: 99%

A Secreted Tyrosine Kinase Acts in the Extracellular Environment

Bordoli

Yum

Breitkopf

et al. 2014

Cell

113

118

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“…Primers sequences used to amplify these loci are given in Table 1. As noted, the products of all these genes have been shown to regulate either the cell cycle or ECM (Prockop 1985;Chen et al 1989;Tonini et al 1991;Apte et al 1994;Lee et al 1995;Matsuoka et al 1995). We assessed expression levels of these genes at three different time points, namely E10.5 (early placentation), E13.5 (mid-placentation) and E16 (after placental maturation).…”

Section: Microarray Analysismentioning

confidence: 99%

“…We assessed changes in the expression levels of these genes, including Col1a2, Col3a1, Timp1, Timp2 and Timp3, using real-time quantitative RT-PCR assays and semiquantitative radioactive RT-PCR. The procollagen gene family is involved in numerous aspects of matrix stability and development (Prockop 1985). The specific genes identified in our screen include Col1a2 (type I procollagen) and Col3a1 (type III procollagen).…”

Section: Reduced Expression Of Hybrid Ecm Genesmentioning

confidence: 99%

“…Collagens are typically secreted by differentiated cells and are formed from procollagen polypeptides (Prockop 1985). To assess the correlation between the observed reduction in procollagen gene expression and the extent of the collagen protein content across the placenta, we performed histological staining with the type I collagen antibody.…”

Section: Histology Reveals Altered Collagen Expression Profilementioning

confidence: 99%

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Changes in cell cycle and extracellular matrix gene expression during placental development in deer mouse (Peromyscus) hybrids

Duselis

Obergfell

Mack

et al. 2007

Reprod. Fertil. Dev.

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Abstract.Crosses between two species of the rodent genus Peromyscus produce defects in both growth and development. The defects are pronounced in the hybrid placentas. Peromyscuys maniculatus (strain BW) females mated to P. polionotus (strain PO) males produce placentas half the size of the parental species, as well as growth-retarded embryos. In contrast, PO females mated to BW males result in defective conceptuses that display embryonic and placental overgrowth. These 'parent-of-origin'-dependent phenotypes are consistent with previous studies that demonstrated altered expression of imprinted genes and genetic linkage of the overgrowth phenotypes to imprinted domains. In the present study, we take a broader approach in assessing perturbations in hybrid placental gene expression through the use of Mus musculus cDNA microarrays. In verifying classes of genes identified in microarray screens differentially regulated during hybrid placental development, we focused on those influencing the cell cycle and extracellular matrix (ECM). Our work suggests that cell cycle regulators at the G 1 /S phase check-point are downregulated in the large hybrid placenta, whereas the small hybrid placenta is more variable. The ECM genes are typically downstream targets of cell cycle regulation and their misregulation is consistent with many of the dysmorphic phenotypes. Thus, these data suggest imbalances in proliferation and differentiation in hybrid placentation.

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“…An alternative approach would be to introduce mutations into the collagen molecule that would render it resistant to cleavage by collagenase. Many inherited or spontaneous mutations in humans that lead to alterations in the structure and function of collagen have been described (6)(7)(8)(9)(10)(11), but none has been reported that results in altered susceptibility to collagenase cleavage.…”

mentioning

confidence: 99%

Generation of collagenase-resistant collagen by site-directed mutagenesis of murine pro alpha 1(I) collagen gene.

Byrne

Stacey

et al. 1990

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

120

117

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Collagenase (matrix metalloproteinase 1) cleaves type I, II, and III collagen helices at a specific site between Gly-Ile or Gly-Leu bonds (residues 775 and 776, Pj-P1'). To understand the mechanism of collagen processing, mutations around the cleavage site have been introduced into the cloned murine proal(I) collagen (Collal) The collagenases cleave native type I, II, and III collagens by hydrolyzing the peptide bond between residues Gly-Ile (or Leu) located at residues 775 and 776 of the helical portion of the al(I) chain to yield a larger three-quarter length fragment (TCA) and a smaller one-quarter length fragment (TCB) (1,4,17). The region around the cleavage site is more hydrophobic than other parts of the collagen molecule and deficient in the hydroxyproline and proline residues that stabilize the triple helix. Our 5888The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Mutations in collagen genes. Consequences for rare and common diseases.

Cited by 40 publications

References 26 publications

A Secreted Tyrosine Kinase Acts in the Extracellular Environment

A Secreted Tyrosine Kinase Acts in the Extracellular Environment

Changes in cell cycle and extracellular matrix gene expression during placental development in deer mouse (Peromyscus) hybrids

Generation of collagenase-resistant collagen by site-directed mutagenesis of murine pro alpha 1(I) collagen gene.

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