- Email: [email protected]
Cloning and sequencing of the cDNA encoding the murine mammary gland long-form prolactin receptor
Gene, 134 (1993) 263-265 Elsevier Science Publishers
263
B.V.
GENE 07447
Cloning and sequencing of the cDNA encoding the murine mammary gland long-form prolactin receptor* (Mus musculus; hphage
library;
RT-PCR;
Robert C. Moore and Takami
recombinant
DNA)
Oka
Laboratory ofMolecular and Cellular Biology, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 8, Room 319. 9000 Rockoille Pike, Bethesda, MD 20892, USA Received by J. Piatigorsky:
8 April 1993; Revised/Accepted:
28 June 1993; Received at publishers:
23 July 1993
SUMMARY
The nucleotide sequence of a 1992-bp cDNA encoding the long form of the murine (PRL-R) has been determined. The deduced 68-kDa protein has high sequence identity receptors from rat ovary and rabbit mammary gland.
INTRODUCTION
Prolactin is a peptide hormone which has multiple biological functions including the regulation of milk production in the mammary gland. The effect of PRL is mediated by the interaction of the hormone and its plasma membrane receptor. Both short and long forms of PRL-R cDNA have been identified that appear to be the result of alternative splicing of transcripts. cDNAs encoding three PRL-R short forms from mouse liver (Davis and Linzer, 1989) and rat liver (Boutin et al., 1989) have been cloned. Long form PRL-R cDNAs have been isolated from rat (Shirota et al., 1990), rabbit (Edery et al., 1989), bovine (Scott et al., 1992) and the human hepatoma cell line HepG2 (Boutin et al., 1989). Mammary Correspondence to: Dr. T. Oka, Laboratory Biology, National Institute of Diabetes,
of Molecular and Digestive
and Cellular and Kidney
Diseases, National Institutes of Health, Building 8, Room 319, 9000 Rockville Pike, Bethesda, MD 20892, USA. Tel. (l-301) 496-1404; Fax (l-301) 402-0053; e-mail: [email protected] *On request, the authors will supply detailed experimental the conclusions reached in this Short Communication.
evidence
for
Abbreviations: aa, amino acid(s); bp, base pairs(s); kb, kilobase or 1000 bp; nt, nucleotide(s); PCR, polymerase chain reaction; PRL, prolactin; PRL-R, PRL receptor(s); RT-PCR, reverse transcriptase-PCR; TM. transmembrane.
mammary prolactin receptor with long forms of prolactin
glands of lactating mice produce the highest level of long form PRL-R mRNA, compared to those of virgin and pregnant mice (Nishikawa et al., 1993). Transfection experiments have shown that the long form of PRL-R from rabbit mammary gland is capable of transducing a signal to milk protein genes (Lesueur et al., 1991) while the role of the short form has yet to be determined.
EXPERIMENTAL
AND DISCUSSION
(a) Isolation of mouse mammary gland long form PRL-R cDNA A mouse mammary gland library was prepared from mRNA purified from a lactating C3H mouse. A cDNA encoding the long form of PRL-R was isolated and its nt sequence determined. A comparison of the deduced aa sequences of the mouse mammary and rat ovary PRL-R suggested that the cDNA clone lacked seven nt of the Send of the open reading frame. A DNA fragment containing part of the 5’-untranslated region and the first 802 bp of the PRL-R coding region was amplified by RT-PCR and used to construct a full length PRL-R cDNA. The deduced mouse mammary PRL-R precursor consists of a polypeptide of 608 aa. Analysis of this sequence by the method of von Heijne (1986) predicts that the PRL-R
264
I”SII”“E~LISSPGDTLGSF‘GKAG~NV~K~SE~AGSGE GTGG~TGTGCMGMCGGGCUGCTTCCCTTCT~~~~~TCT~GGC~~CTCC~~G~~~TTGTCTATGCT~CCCC~~~TACGTG~~TT~C VAVGEGAKSFPSDKPWTSYPPLGEKGPIVYAKPPD~VEIH ~GTCMC~OLCGWIGTGCTATCATTACTCCC~G~~~~CUCCA~~~CCCTGGGGTTCCT~CCAGTMG~GTATGC~GGTATCTGGGGT~~~T K~NKDGVLSLLPKGRENHGTENPGVPETSKEVAKVSGVTLI AA~AICAT~~TGGTGTTAGTGC~GACTCACGAGCCCA~CA~GCTTTGCTT~G~TCAGCCMGMGGTTCCACCATCGCTT~~~CCMTCTGAG~~TCTGGCCAGC RNILVLVPDSRAGNTALLEESAKKVPPSLE~R~~EKGLAS TTTA~TG~~~T~~GWUCTGCAWCTCCMCTCCMCTGGG~GGCTG~TTACCTG~TCCTACGTGCTTCATG~CTCCTTT~CTGA~GCTA~CTTAT~CA~TT~CT~T~ F TATS S N C R L G L G R L D V CD P T C F NH S F H 1**
1:: 540 1798 580 1918 608
W\TTTCTCTTUCGTMCACTA~~GT~T~GTMTGTGGTCTGCTM~TGTTA~G~TGTG~TAT
1992
Fig. I. The nt sequence Three asterisks indicate
of the mouse mammary a stop codon. GenBank
PRL-R cDNA and the deduced aa sequence. Sequence encoding predicted TM region is underlined. accession number is L13593. The mouse PRL-R sequence was obtained by: (a) isolation of a clone
(RM236) from a mouse mammary cDNA library constructed in kZAPl1 using a 32P-labeled PCR fragment encoding the receptor intracellular domain; (b) sequencing RM236 after phagemid rescue using helper phage R408; (c) RT-PCR amplification of the missing 5’-end of the coding region using mammary RNA and primers to the 5’-untranslated region of mouse liver PRL-R (Davis and Linzer, 1989) and RM236 coding sequence; (d) exchange of restriction fragments to create RM252 and sequencing using long form specific primers confirmed the sequence and identity
the complete nt sequence of clone RM252. Additional RT-PCR experiments of the 5’-end of the cDNA. Methods: PRL-R cDNA was amplified in a final
volume of 100 pi in a I x PCR buffer (50 mM KCljlO mM TrisHCI (pH 8.3)/1.5 mM MgCl,) containing 0.2 mM each dNTPjlO0 ng each primer/phage h cDNA/2.5 units of Taq polymerase. A 1217-bp PRL-R probe was synthesized by amplifying AZAPII library cDNA with PRL-R specific upstream primer 8 (T-TATCTTGTCCAGACTCGCTGCAAGC) and downstream primer 12 (S-CACGTAGGATCCAGGTAATCCAGCC). The PCR program was as follows: denaturation at 94-C for 1 min, annealing of primers at 60°C for 1min and elongation at 72°C for 2 min. cDNA was synthesized from mammary gland total RNA in a final volume of 20 ~1 in a I x PCR buffer containing 1 mM each dNTP/l unit of RNase inhibiter/5.2 pg total RNA/random hexamers (2.5 pM112.5 units of Moloney Murine leukemia virus RT (Perkins Elmer Cetus). PRL-R cDNA was amplified using upstream primer 24 (5’-GATCTAGAGAAGGGAGCCTCTGATCTATTGCCT) and downstream primer 25 (S-GATCTAGACAGGAACTGGTGGAAAGATGCAGGT) or downstream primer 68 (5’-ACTTCCAAGAATTCCACCAGCAAGT). Primers 24 and 25 contain a 5’-XbaI site and primer 68 contains a single nt mutation (C-*T) to introduce an EcoRI site to facilitate cloning. PRL-R cDNA was amplified by PCR as described
above.
contains a 19-aa signal sequence. The mature receptor is composed of 589 aa with a 210”aa extracellular domain, a single 24-aa transmembrane (TM) region and a 355-aa cytoplasmic domain (Fig. 1). The 3’-untranslated region of the mouse mammary PRL-R cDNA sequence does not ~onseusus have the polyadenylation SHp_li?Il~~ (AATAAA), as was the case with the rat ovary (Shirota et al., 1990) and bovine (Scott et al., 1992) PRL-R cDNA sequences. (b) Sequence analysis Long and short forms of PRL-R have highly conserved extracellular and TM domains; i.e., the first 280 aa of the PRL-R long form are identical to the mouse liver short form. Among long forms, the mouse mammary receptor shares 91% (of 610 aa) and 72% (of 616 aa) identity with rat and rabbit receptors, respectively. The most conserved region of the cytoplasm& domains of all forms of PRLR is adjacent to the TM region. All differences in peptide sequence of the mature PRL-R that are due to the addition or deletion of aa are clustered within the central
region of the intracellular domain, from aa 384 to 524 (Fig. 2). This variable region of the receptor appears to be dispensable because the PRL-R of the Nb2 rat lymphoma cell line, which lacks this region, is still capable of stimulating milk protein gene expression (Ali et al.,
$8” Rt P.B B0 Hu
N”“*IPPTPNPQ*l++xNNTPNCHTDTSRSTTWP*”LP”P *****GTN..F.V.RP..S...**.L*....“P......”........ .***....vD.. .**‘VTH.WD..TISLVDREI.YLGVNO...G...L”.Q*....NTN....N...~....T .‘**LTCLQA..STSMGKI.YFLANGP..S...FPQ.*.SLYSP.YS..N.....E..L THTWD.PCISHg**~'"GKI.YF.AGG..CS...*"..Q.S..NP..S..N.T...E..V
SO Hu
GHAG.TATS..QT~HA."**.A.KTIET.R.GK.TX*Q*RBSEGC.S'.PD.D.V..RP G.AGAPATL.M(.CMA.g**.S.~IKSR..GX.T.+QREW..H.ETD"*.D.P.LLP
f$
QEKGPIVYAKPPDYVEIHKDGVLSLLPKQREN*HQTENPG . ..S.T..V...................F......'N...K.. K..P.FISP..L............A....L..K..GD..GKA. .D.T.LIS...tE.......SQ....A.F...N.R*P*****. . ..T.FGS...L............A..........SGKPKK..
Rb BO nu
524 526 532 535 538
Fig. 2. Comparison of variable regions in the intracellular domains of long form PRL-R. Deduced aa 384-524 of mouse (Mu) mammary PRLR is compared to corresponding aa of rat (Rt) ovary (Shirota et al., 1990), rabbit (Rb) mammary gland (Edery et al., 1989), bovine (Bo) (Scott et al., 1992) and human (Hu) HepG2 cell (Boutin et al., 1989) PRL-R. Dot indicates identical aa, asterisk indicates addition or deletion of aa.
265 1991; 1992). The
cDNA
useful
in determining
mouse
mammary
scription
(c) Conclusions We have isolated PRL-R
described
the domains
will be
which
regulates
the
the tran-
genes.
and sequenced
the mouse mammary
PRL-R cDNA. The mouse mammary
is homologous
to long forms of PRL-R
is the least conserved
Kelly, P.A.: The Nb2 form of prolactin a milk protein
gene promoter.
Boutin, J.M., Jolicoeur, Shirota, M., Banville,
receptor
Mol. Endocrinol.
is able to activate 6 (1992) 1242-1248.
C., Okamura, H., Gagnon, J., Edery, M., D., Dusanter-Fourt, I., Djiane, J. and Kelly,
P.A.: Cloning and expression of the rat prolactin receptor, a member of the growth hormone/prolactin receptor gene family. Cell 8 (1988) 69977. Boutin, J.M., Edery, M., Shirota, M., Jolicoeur, C., Lesuer, L., Ah, S.,
rabbit, bovine and human. The central 384-524) of the mouse mammary PRL-R domain
here
through
long form PRL-R
of milk protein
long form of the
clone
among
from rat,
region (aa intracellular
the long forms of
Gould, D., Djiane, J. and Kelly, P.A.: Identification of a cDNA encoding a long form of prolactin receptor in human hepatoma and breast cancer cells. Mol. Endocrinol. 3 (1989) 1455-1461. Davis, J.A. and Linzer, D.I.: Expression of multiple forms of the prolactin receptor in mouse liver. Mol. Endocrinol. 3 (1989) 6744680. Edery, M., Jolicoeur, C., Levi, M.C., Dusanter, F.I., Pttridou, B., Boutin, J.M., Lesueur, L., Kelly, P.A. and Djiane, J.: Identification and sequence analysis of a second form of prolactin receptor by molecular cloning of complementary DNA from rabbit mammary gland. Proc.
PRL-R.
Natl. Acad. Sci. USA 86 (1989) 2112-2116.
ACKNOWLEDGEMENTS
We would like to thank Drs. Lee Burns, Roland Owens and Frank Tietze for critical reading of the manuscript. We also thank Drs. Norio Nonomura and Seiji Nishikawa for their helpful suggestions.
Lesueur, L., Edery, M., Ah, S., Paly, J., Kelly, P.A. and Djiane, J.: Comparison of long and short forms of the prolactin receptor on prolactin-induced milk protein gene transcription. Proc. Natl. Acad. Sci. USA 88 (1991) 8244828. Nishikawa, S., Moore, R.C., A. Kanai and Oka, T.: Hormonal regulation of long form prolactin receptor mRNA and its relationship to B-casein gene expression in the mouse mammary gland. Endocrine J. (1993) in press. Scott, P.I., Kessler, M.A. and Schuler, L.A.: Molecular cloning of the bovine prolactin receptor and distribution of prolactin and growth hormone receptor transcripts in fetal and Mol. Cell. Endocrinol. 89 (1992) 47-58.
REFERENCES Ah, S., Pellegrini, I. and Kelly, P.A.: A prolactin-dependent immune cell line (Nb2) expresses a mutant form of prolactin receptor. _I.Biol. Chem.266(1991)20110-20117. Ali, S., Edery, M., Pellegrini,
I., Lesueur,
L., Paly, J., Djiane,
J. and
utero-placental
tissues.
Shirota, M., Banville, D., Ali, S., Jolicoeur, C., Boutin, J.M., Edery, M., Djiane, J. and Kelly, P.A.: Expression of two forms of prolactin receptor in rat ovary and liver. Mol. Endocrinol. 4 (1990) 1136-l 143. von Heijne, G.: A new method for predicting signal sequence sites. Nucleic Acids Res. 14 (1986) 4683-4690.
cleavage
263
B.V.
GENE 07447
Cloning and sequencing of the cDNA encoding the murine mammary gland long-form prolactin receptor* (Mus musculus; hphage
library;
RT-PCR;
Robert C. Moore and Takami
recombinant
DNA)
Oka
Laboratory ofMolecular and Cellular Biology, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 8, Room 319. 9000 Rockoille Pike, Bethesda, MD 20892, USA Received by J. Piatigorsky:
8 April 1993; Revised/Accepted:
28 June 1993; Received at publishers:
23 July 1993
SUMMARY
The nucleotide sequence of a 1992-bp cDNA encoding the long form of the murine (PRL-R) has been determined. The deduced 68-kDa protein has high sequence identity receptors from rat ovary and rabbit mammary gland.
INTRODUCTION
Prolactin is a peptide hormone which has multiple biological functions including the regulation of milk production in the mammary gland. The effect of PRL is mediated by the interaction of the hormone and its plasma membrane receptor. Both short and long forms of PRL-R cDNA have been identified that appear to be the result of alternative splicing of transcripts. cDNAs encoding three PRL-R short forms from mouse liver (Davis and Linzer, 1989) and rat liver (Boutin et al., 1989) have been cloned. Long form PRL-R cDNAs have been isolated from rat (Shirota et al., 1990), rabbit (Edery et al., 1989), bovine (Scott et al., 1992) and the human hepatoma cell line HepG2 (Boutin et al., 1989). Mammary Correspondence to: Dr. T. Oka, Laboratory Biology, National Institute of Diabetes,
of Molecular and Digestive
and Cellular and Kidney
Diseases, National Institutes of Health, Building 8, Room 319, 9000 Rockville Pike, Bethesda, MD 20892, USA. Tel. (l-301) 496-1404; Fax (l-301) 402-0053; e-mail: [email protected] *On request, the authors will supply detailed experimental the conclusions reached in this Short Communication.
evidence
for
Abbreviations: aa, amino acid(s); bp, base pairs(s); kb, kilobase or 1000 bp; nt, nucleotide(s); PCR, polymerase chain reaction; PRL, prolactin; PRL-R, PRL receptor(s); RT-PCR, reverse transcriptase-PCR; TM. transmembrane.
mammary prolactin receptor with long forms of prolactin
glands of lactating mice produce the highest level of long form PRL-R mRNA, compared to those of virgin and pregnant mice (Nishikawa et al., 1993). Transfection experiments have shown that the long form of PRL-R from rabbit mammary gland is capable of transducing a signal to milk protein genes (Lesueur et al., 1991) while the role of the short form has yet to be determined.
EXPERIMENTAL
AND DISCUSSION
(a) Isolation of mouse mammary gland long form PRL-R cDNA A mouse mammary gland library was prepared from mRNA purified from a lactating C3H mouse. A cDNA encoding the long form of PRL-R was isolated and its nt sequence determined. A comparison of the deduced aa sequences of the mouse mammary and rat ovary PRL-R suggested that the cDNA clone lacked seven nt of the Send of the open reading frame. A DNA fragment containing part of the 5’-untranslated region and the first 802 bp of the PRL-R coding region was amplified by RT-PCR and used to construct a full length PRL-R cDNA. The deduced mouse mammary PRL-R precursor consists of a polypeptide of 608 aa. Analysis of this sequence by the method of von Heijne (1986) predicts that the PRL-R
264
I”SII”“E~LISSPGDTLGSF‘GKAG~NV~K~SE~AGSGE GTGG~TGTGCMGMCGGGCUGCTTCCCTTCT~~~~~TCT~GGC~~CTCC~~G~~~TTGTCTATGCT~CCCC~~~TACGTG~~TT~C VAVGEGAKSFPSDKPWTSYPPLGEKGPIVYAKPPD~VEIH ~GTCMC~OLCGWIGTGCTATCATTACTCCC~G~~~~CUCCA~~~CCCTGGGGTTCCT~CCAGTMG~GTATGC~GGTATCTGGGGT~~~T K~NKDGVLSLLPKGRENHGTENPGVPETSKEVAKVSGVTLI AA~AICAT~~TGGTGTTAGTGC~GACTCACGAGCCCA~CA~GCTTTGCTT~G~TCAGCCMGMGGTTCCACCATCGCTT~~~CCMTCTGAG~~TCTGGCCAGC RNILVLVPDSRAGNTALLEESAKKVPPSLE~R~~EKGLAS TTTA~TG~~~T~~GWUCTGCAWCTCCMCTCCMCTGGG~GGCTG~TTACCTG~TCCTACGTGCTTCATG~CTCCTTT~CTGA~GCTA~CTTAT~CA~TT~CT~T~ F TATS S N C R L G L G R L D V CD P T C F NH S F H 1**
1:: 540 1798 580 1918 608
W\TTTCTCTTUCGTMCACTA~~GT~T~GTMTGTGGTCTGCTM~TGTTA~G~TGTG~TAT
1992
Fig. I. The nt sequence Three asterisks indicate
of the mouse mammary a stop codon. GenBank
PRL-R cDNA and the deduced aa sequence. Sequence encoding predicted TM region is underlined. accession number is L13593. The mouse PRL-R sequence was obtained by: (a) isolation of a clone
(RM236) from a mouse mammary cDNA library constructed in kZAPl1 using a 32P-labeled PCR fragment encoding the receptor intracellular domain; (b) sequencing RM236 after phagemid rescue using helper phage R408; (c) RT-PCR amplification of the missing 5’-end of the coding region using mammary RNA and primers to the 5’-untranslated region of mouse liver PRL-R (Davis and Linzer, 1989) and RM236 coding sequence; (d) exchange of restriction fragments to create RM252 and sequencing using long form specific primers confirmed the sequence and identity
the complete nt sequence of clone RM252. Additional RT-PCR experiments of the 5’-end of the cDNA. Methods: PRL-R cDNA was amplified in a final
volume of 100 pi in a I x PCR buffer (50 mM KCljlO mM TrisHCI (pH 8.3)/1.5 mM MgCl,) containing 0.2 mM each dNTPjlO0 ng each primer/phage h cDNA/2.5 units of Taq polymerase. A 1217-bp PRL-R probe was synthesized by amplifying AZAPII library cDNA with PRL-R specific upstream primer 8 (T-TATCTTGTCCAGACTCGCTGCAAGC) and downstream primer 12 (S-CACGTAGGATCCAGGTAATCCAGCC). The PCR program was as follows: denaturation at 94-C for 1 min, annealing of primers at 60°C for 1min and elongation at 72°C for 2 min. cDNA was synthesized from mammary gland total RNA in a final volume of 20 ~1 in a I x PCR buffer containing 1 mM each dNTP/l unit of RNase inhibiter/5.2 pg total RNA/random hexamers (2.5 pM112.5 units of Moloney Murine leukemia virus RT (Perkins Elmer Cetus). PRL-R cDNA was amplified using upstream primer 24 (5’-GATCTAGAGAAGGGAGCCTCTGATCTATTGCCT) and downstream primer 25 (S-GATCTAGACAGGAACTGGTGGAAAGATGCAGGT) or downstream primer 68 (5’-ACTTCCAAGAATTCCACCAGCAAGT). Primers 24 and 25 contain a 5’-XbaI site and primer 68 contains a single nt mutation (C-*T) to introduce an EcoRI site to facilitate cloning. PRL-R cDNA was amplified by PCR as described
above.
contains a 19-aa signal sequence. The mature receptor is composed of 589 aa with a 210”aa extracellular domain, a single 24-aa transmembrane (TM) region and a 355-aa cytoplasmic domain (Fig. 1). The 3’-untranslated region of the mouse mammary PRL-R cDNA sequence does not ~onseusus have the polyadenylation SHp_li?Il~~ (AATAAA), as was the case with the rat ovary (Shirota et al., 1990) and bovine (Scott et al., 1992) PRL-R cDNA sequences. (b) Sequence analysis Long and short forms of PRL-R have highly conserved extracellular and TM domains; i.e., the first 280 aa of the PRL-R long form are identical to the mouse liver short form. Among long forms, the mouse mammary receptor shares 91% (of 610 aa) and 72% (of 616 aa) identity with rat and rabbit receptors, respectively. The most conserved region of the cytoplasm& domains of all forms of PRLR is adjacent to the TM region. All differences in peptide sequence of the mature PRL-R that are due to the addition or deletion of aa are clustered within the central
region of the intracellular domain, from aa 384 to 524 (Fig. 2). This variable region of the receptor appears to be dispensable because the PRL-R of the Nb2 rat lymphoma cell line, which lacks this region, is still capable of stimulating milk protein gene expression (Ali et al.,
$8” Rt P.B B0 Hu
N”“*IPPTPNPQ*l++xNNTPNCHTDTSRSTTWP*”LP”P *****GTN..F.V.RP..S...**.L*....“P......”........ .***....vD.. .**‘VTH.WD..TISLVDREI.YLGVNO...G...L”.Q*....NTN....N...~....T .‘**LTCLQA..STSMGKI.YFLANGP..S...FPQ.*.SLYSP.YS..N.....E..L THTWD.PCISHg**~'"GKI.YF.AGG..CS...*"..Q.S..NP..S..N.T...E..V
SO Hu
GHAG.TATS..QT~HA."**.A.KTIET.R.GK.TX*Q*RBSEGC.S'.PD.D.V..RP G.AGAPATL.M(.CMA.g**.S.~IKSR..GX.T.+QREW..H.ETD"*.D.P.LLP
f$
QEKGPIVYAKPPDYVEIHKDGVLSLLPKQREN*HQTENPG . ..S.T..V...................F......'N...K.. K..P.FISP..L............A....L..K..GD..GKA. .D.T.LIS...tE.......SQ....A.F...N.R*P*****. . ..T.FGS...L............A..........SGKPKK..
Rb BO nu
524 526 532 535 538
Fig. 2. Comparison of variable regions in the intracellular domains of long form PRL-R. Deduced aa 384-524 of mouse (Mu) mammary PRLR is compared to corresponding aa of rat (Rt) ovary (Shirota et al., 1990), rabbit (Rb) mammary gland (Edery et al., 1989), bovine (Bo) (Scott et al., 1992) and human (Hu) HepG2 cell (Boutin et al., 1989) PRL-R. Dot indicates identical aa, asterisk indicates addition or deletion of aa.
265 1991; 1992). The
cDNA
useful
in determining
mouse
mammary
scription
(c) Conclusions We have isolated PRL-R
described
the domains
will be
which
regulates
the
the tran-
genes.
and sequenced
the mouse mammary
PRL-R cDNA. The mouse mammary
is homologous
to long forms of PRL-R
is the least conserved
Kelly, P.A.: The Nb2 form of prolactin a milk protein
gene promoter.
Boutin, J.M., Jolicoeur, Shirota, M., Banville,
receptor
Mol. Endocrinol.
is able to activate 6 (1992) 1242-1248.
C., Okamura, H., Gagnon, J., Edery, M., D., Dusanter-Fourt, I., Djiane, J. and Kelly,
P.A.: Cloning and expression of the rat prolactin receptor, a member of the growth hormone/prolactin receptor gene family. Cell 8 (1988) 69977. Boutin, J.M., Edery, M., Shirota, M., Jolicoeur, C., Lesuer, L., Ah, S.,
rabbit, bovine and human. The central 384-524) of the mouse mammary PRL-R domain
here
through
long form PRL-R
of milk protein
long form of the
clone
among
from rat,
region (aa intracellular
the long forms of
Gould, D., Djiane, J. and Kelly, P.A.: Identification of a cDNA encoding a long form of prolactin receptor in human hepatoma and breast cancer cells. Mol. Endocrinol. 3 (1989) 1455-1461. Davis, J.A. and Linzer, D.I.: Expression of multiple forms of the prolactin receptor in mouse liver. Mol. Endocrinol. 3 (1989) 6744680. Edery, M., Jolicoeur, C., Levi, M.C., Dusanter, F.I., Pttridou, B., Boutin, J.M., Lesueur, L., Kelly, P.A. and Djiane, J.: Identification and sequence analysis of a second form of prolactin receptor by molecular cloning of complementary DNA from rabbit mammary gland. Proc.
PRL-R.
Natl. Acad. Sci. USA 86 (1989) 2112-2116.
ACKNOWLEDGEMENTS
We would like to thank Drs. Lee Burns, Roland Owens and Frank Tietze for critical reading of the manuscript. We also thank Drs. Norio Nonomura and Seiji Nishikawa for their helpful suggestions.
Lesueur, L., Edery, M., Ah, S., Paly, J., Kelly, P.A. and Djiane, J.: Comparison of long and short forms of the prolactin receptor on prolactin-induced milk protein gene transcription. Proc. Natl. Acad. Sci. USA 88 (1991) 8244828. Nishikawa, S., Moore, R.C., A. Kanai and Oka, T.: Hormonal regulation of long form prolactin receptor mRNA and its relationship to B-casein gene expression in the mouse mammary gland. Endocrine J. (1993) in press. Scott, P.I., Kessler, M.A. and Schuler, L.A.: Molecular cloning of the bovine prolactin receptor and distribution of prolactin and growth hormone receptor transcripts in fetal and Mol. Cell. Endocrinol. 89 (1992) 47-58.
REFERENCES Ah, S., Pellegrini, I. and Kelly, P.A.: A prolactin-dependent immune cell line (Nb2) expresses a mutant form of prolactin receptor. _I.Biol. Chem.266(1991)20110-20117. Ali, S., Edery, M., Pellegrini,
I., Lesueur,
L., Paly, J., Djiane,
J. and
utero-placental
tissues.
Shirota, M., Banville, D., Ali, S., Jolicoeur, C., Boutin, J.M., Edery, M., Djiane, J. and Kelly, P.A.: Expression of two forms of prolactin receptor in rat ovary and liver. Mol. Endocrinol. 4 (1990) 1136-l 143. von Heijne, G.: A new method for predicting signal sequence sites. Nucleic Acids Res. 14 (1986) 4683-4690.
cleavage