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[Pre-adipocyte factor-1] Pref-1 has been characterized as a transmembrane glycoprotein with six copies of an EGF-like repeat. Multiple pref-1 transcripts are generated by alternate splicing. In pre-adipocytes, multiple forms of the protein arise from various post-translational modifications (Smas and Sul, 1993; Smas et al, 1994). The protein has been described independently as pG2, FA-1 [Fetal antigen-1], and delta-like and sequence analysis has demonstrated that these proteins arise from the same gene (Lee et al, 1995).
Pref-1 mRNA is expressed abundantly in pre-adipocytes and its expression is abolished completely during differentiation of 3T3-L1 pre-adipocytes to adipocytes. Constitutive expression of pref-1 in pre-adipocytes inhibits adipose differentiation. A soluble form of pref-1 consisting of its processed ectodomain has been described (Smas et al, 1997). pref-1 can thus inhibit differentiation of adipocytes in a juxtacrine or paracrine way. The differentiation of adipocytes is modulated by secreted variants of the proteins and requires the expression of membrane-associated forms (Garces et al, 1999). Mei et al (2002) have reported that proteolytic processing of Pref-1 at two sites in the extracellular domain yields a larger (50 kDa) that is responsible for inhibition of adipocyte differentiation and a smaller (25 kDa) soluble form that is not inhibitory.
pref-1 may have a broader role in differentiation and development as demonstrated by its expression in embryonic tissues, tumors, and a stromal cell line (see: delta-like). Tanimizu et al (2003) have reported that Pref-1 is a useful marker to enrich highly proliferative hepatoblasts from fetal liver.
An endocrine mode of action of soluble Pref-1 is suggested by studies of transgenic mice expressing the soluble 50 kDa form. These mice show a substantial decrease in total fat pad weight, reduced expression of markers characteristic of adipocytes and adipocyte-secreted factors, including leptin and adiponectin, hypertriglyceridemia, impaired glucose tolerance, and decreased insulin sensitivity (Lee et al, 2003).
Activities that go beyond the involvement in the differentiation of adipocytes has been revealed by the study of knock-out mice lacking expression of Pref-1. These animals are characterized by accelerated fat deposition, perinatal mortality and growth retardation and skeletal malformations (Villena et al, 2002).
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ENTRY LAST MODIFIED: August 2004
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