Nucleotide sequence of a growth-related mRNA encoding a member of the prolactin-growth hormone family.

Abstract

As part of the proliferative response to serum, mouse 3T3 cells produce a set of growth-related mRNAs identified by hybridization to cloned cDNAs. One of these mRNAs, which is about 1 kilobase long, appears within a few hours after stimulation of resting cells with serum or plateletderived growth factor and reaches a high level during the transition from the GI to the S phase of growth. This mRNA is translated in vitro into a protein of approximately 25 kilodaltons. The corresponding cloned cDNA of 791 base pairs has been sequenced; it contains a single open reading frame that encodes a protein of 224 amino acids with extensive sequence homology to mammalian prolactins. The initial 29-amino acid segment of the encoded protein resembles the signal sequences of prehormones. That the growth-related protein is not mouse prolactin is indicated by comparison of its predicted amino acid composition with that of mouse prolactin and by the distinct fragment patterns seen when restricted mouse DNA is probed with the cloned cDNA or rat prolactin cDNA. Therefore, the growth-related protein appears to be a new member of the prolactin-growth hormone family. Because of its relationship to prolactin and growth hormone and its association with cell proliferation, the protein has been called "proliferin."Activation of specific genes occurs during the transition of mammalian cells from the resting to the growing state (1). What these genes are and what roles the products of these genes play in the progression of the cell cycle remain, for the most part, to be elucidated. Recently, several groups of workers have reported the molecular cloning of cDNAs corresponding to growth-related mRNAs from cultured mouse cells stimulated with serum or purified growth factors (2-4). One of the growth-related mRNAs that we found in a number of proliferating murine cell lines is a 1-kilobase RNA (referred to as 28H6) that is virtually undetectable in nongrowing cells (2, 5). Following serum stimulation of BALB/c 3T3 fibroblastic cells, 28H6 RNA appears within 3 hr and reaches a maximal level at the time of transition between the G1 and S phases of growth. Because 28H6 RNA is not always found in proliferating murine cell lines (2, 5), its expression is not essential for growth. However, our interest in this RNA was reinforced when nucleotide sequence analysis of an incomplete cDNA clone suggested that 28H6 RNA encoded a protein related to prolactin (2,5). We now report the sequence of a cDNA clone that appears to contain the complete coding and 3'-untranslated regions of the mRNA. This cDNA encodes a protein of 224 amino acids with extensive homology to mammalian prolactins. By several criteria the encoded protein is likely to be a new member of the prolactin-growth hormone family. Because of its relationship to prolactin and growth hormone and its association with cell proliferation, the protein will be referred to as "proliferin" or "PLF." MATERIALS AND METHODSDNA Sequence Analysis. The cDNA clones were end labeled by filling in 5' overha...

cDNA cloning of somatolactin, a pituitary protein related to growth hormone and prolactin.

“…Somatolactin is also distantly related to mouse proliferin (23% identity; ref. 22), a placental protein distantly related to GH and PRL. From the foregoing, we conclude that somatolactin is a pituitary protein belonging to the GH/PRL family but clearly distinct from GH, PRL, PL, and proliferin.…”

Cell-cycle-specific and serum-dependent expression of gamma-actin mRNA in Swiss mouse 3T3 cells.

“…Cochran et al (7) reported on five platelet-derived growth factor-inducible genes in BALB/c mouse 3T3 cells. Nathan's group reported on the expression of several genes which are activated soon after resting BALB/c 3T3 cells are stimulated with serum or plateletderived growth factor (16,17,(19)(20)(21). One of these genes, called proliferin, belongs to the prolactin growth hormone family (19).…”

A growth-responsive gene (16C8) in normal mouse fibroblasts homologous to a human collagenase inhibitor with erythroid-potentiating activity: evidence for inducible and constitutive transcripts

“…1B Fig. 2), which has recently been shown to be identical to proliferin (23), a member of a prolactin-like family of secreted proteins (28). Analysis of the sequence of 16C8 revealed a reading frame capable of encoding a protein of Mr 22,500; the sequence of this protein is shown in Fig.…”