Elsevier

Matrix Biology

Volume 15, Issue 7, March 1997, Pages 479-493
Matrix Biology

Human fibulin-1D: Molecular cloning, expression and similarity with S1–5 protein, a new member of the fibulin gene family

https://doi.org/10.1016/S0945-053X(97)90021-4Get rights and content

Abstract

Fibulin-1 is an extracellular matrix (ECM) component of basement membranes and connective tissue elastic fibers, and a blood protein. Multiple forms of fibulin-1 that differ in their C-terminal regions are produced through the process of alternative splicing of their precursor RNA. Two transcripts of 2.4 and 2.7 kb are the predominant fibulin-1 mRNAs expressed in human tissues and cultured cells. While the 2.4 kb transcript had been shown to encode fibulin-1C, the 2.7 kb transcript did not correspond to any of the previously identified human fibulin-1 variants. Here in, we report on the isolation and sequencing of cDNA corresponding to the 2.7 kb fibulin-1 transcript which encodes a novel, alternatively spliced form of human fibulin-1 that we term the D form. The deduced amino acid sequence of the D form is identical in its first 566 residues to the three known fibulin-1 variants (fibulin-IA-C); however, it has a unique 137 aminoa cid-C-terminal segment encoded by the alternatively spliced portion of its transcript. RNA hybridization analysis showed that the fibulin-1D transcript is coordinately expressed with that of fibulin-1C both in tissues and in cultured cells. Using antibodies specific to the unique C-terminal segment of fibulin-1D and -1C, both proteins were found to be expressed in human placenta. Recombinant fibulin-1D generated in transfected mammalian cells displayed similar ligand-binding properties as placenta-derived fibulin-1 and recombinant fibulin-1C, and its was capable of incorporating into cultured cell ECM in the absence of other fibulin-1 forms. A comparative sequence analysis revealed that the unique C-terminal region of fibulin-1D is similar to the C-terminal reqions of fibulin-1C and fibulin-2. Furthermore, the C-terminal regions of fibulin-1C, -1D and -2 are similar to the C-terminal region of a recently described protein termed S1–5. In addition to this C-terminal similarity, S1–5 also contains repeated EGF-like modules and a conserved N-terminal element, thereby leading to the conclusion that S1–5 is a third member of the fibulin gene family.

References (28)

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    The 37 amino acid cytoplasmic domain peptide of integrin β1 was coupled to CNBR-activated sepharose beads (GE Biosciences, Pharmacia). Beads were incubated overnight at 4 °C with 5 μg of pFBLN1 or recombinant fibulin-1C (rFBLN1C), purified from conditioned media of transfected HT1080 cells [28], in TBS binding buffer containing 25 mM OG and 1 mM of CaCl2 and MgCl2. The supernatant (unbound fraction) was removed and beads were washed 4 times with binding buffer and 2 × non-reducing sample buffer was added.

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