Development - Prolactin receptor signaling

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Prolactin signaling

Prolactin is a polypeptide hormone secreted by the pituitary gland and to a lesser extent by numerous extrapituitary tissues. This hormone affects a great amount of physiological processes [1]. Numerous biological functions have been attributed to this hormone's activity, ranging from reproduction and lactation to growth and development, from endocrinology and metabolism to brain and behavior, as well as immune regulation [2]. Prolactin is a primary factor required for the growth and terminal differentiation of mammary epithelial cells as determined by the induction of transcription of milk protein genes required for lactation [2], [3].

The initial step in Prolactin action is the binding to specific membrane cytokine receptor, Prolactin receptor [2]. Prolactin receptor has an extracellular ligand-binding domain and intracellular domain. Prolactin is one of a family of related hormones including growth hormones Somatotropin, Lactogen and CSH1 (somatomammotropin A) that also bind to Prolactin receptor [4], [5], [6].

The cytoplasmic domain of the Prolactin receptor displays no enzymatic activity, but signals through activation of associated cytoplasmic tyrosine kinases, such as Janus kinase 2 (JAK2), V-src sarcoma viral oncogene homolog and FYN oncogene related to SRC FGR YES (c-Src and Fyn), NIMA-related kinase 3 (NEK3) and Tec protein tyrosine kinase (TEC) [7], [8], [9], [10], [11].

JAK2 activity stimulates Prolactin receptor dimerization and phosphorylation. Activated receptor through JAK2 recruits Signal transducers and activators of transcription (STAT), in particular STAT1, STAT3 and STAT5 (STAT5A and STAT5B), and stimulates STATs tyrosine phosphorylation. The phosphorylated STATs dimmerize and translocate to the nucleus, resulting in the initiation of transcription of Interferon-regulatory factor-1 (IRF-1) and milk protein genes (such as Beta-casein and Lactoglobulin) in lymphocytes and mammary gland cells, respectively [12], [13], [14].

In the nucleus STATs interact with coactivators CBP (CREB binding protein), p300, and N-myc interactor (NMI) [15], [16]. STAT5 transcriptional activation can be cooperatively enhanced by the alpha form of Nuclear receptor subfamily 3 group C member 1 (GCR-alpha) and CCAAT/Enhancer binding protein-beta (C/EBPbeta) to induce the transcription of Beta-casein gene [17]. Prolactin stimulation of mammary cells leads to the nuclear translocation of Tyrosine phosphatase non-receptor type 11 (SHP-2) as a complex with STAT5A and binding of this complex to DNA, determining the milk protein gene transcription [3], [18].

STAT5 factors also induce the transcription of Cyclin D1 (which regulates cell cycle progression) and the antiapoptotic factor BCL2-like 1 (Bcl-XL) [19], [20].

In response to Prolactin receptor stimulation activated STATs translocate into the nucleus and bind to the interferon-gamma activation sequence (GAS) in the promoter region of target genes. STAT1 and STAT3 have been shown to stimulate the transcription of the immediate early gene IRF-1 in lymphocytes [21], [22], [23]. STAT1 activation of IRF-1 promoter is enhanced by the constitutive factor Sp1 transcription factor (SP1), and coactivators E1A binding protein p300 (p300) and CREB binding protein (CBP) [24], [25].

In response to lymphocyte stimulation transcription factors STAT1 and Nuclear factor kappa B (NF-kB) synergistically activate the IRF-1 promoter, via the GAS and NF-kB elements, respectively [26], [27]. STAT5B has been demonstrated to inhibit the IRF-1 transcription, and this inhibition is dependent upon Prolactin receptor stimulation. STAT5B inhibition does not require binding to the GAS element, but is mediated by squelching of limiting amounts of p300/CBP coactivators necessary for gene transcription [28].

In addition, association of 2',5'-oligoadenylate synthetase (OAS1) with the Prolactin receptor inhibits STAT1 signaling to the IRF-1 promoter [29].

Suppressors of Cytokine Signaling (SOCS) gene expression is mediated by STAT3 and STAT1. SOCS1 and SOCS3 involve in negative regulation of JAK2 and STAT5-dependent Beta-casein transcription [30], [31].

Prolactin receptor dimerization also induces the Mitogen-activated protein kinases pathway via JAK2 and Fyn kinases activation [7], [32], [33]. The complex formations of Fyn/ SHC transforming protein (Shc), Shc/GRB2, and Grb2/Son of sevenless homolog (SOS) induce Shc/GRB2/SOS/v-Ha-ras Harvey rat sarcoma viral oncogene homolog (H-Ras)/Mitogen-activated protein kinase kinase 1 and 2 (MEK1 and MEK2)/Mitogen-activated protein kinase 3/1 (ERK1/2) cascade, ultimately activating Jun oncogene (c-Jun) and c-Myc transcription factors necessary for cell cycle progression [34], [35], [36].

Fyn and JAK2 also activate Phosphatidylinositol-3 kinase (PIK3)/V-akt murine thymoma viral oncogene homolog 1 (AKT(PKB))-pathway leading to cell survival [37], [38], [39]. Fyn phosphorylates regulatory subunit of PIK3 (PIK3 reg class 1A). JAK2 is required for the phosphorylation of insulin receptor substrate IRS-1. The role of IRS-1 is to provide docking sites for PIK3 reg class 1A that activates catalytic subunit (PIK3 cat class 1A) [40]. Adaptor protein c-Cbl, which is phosphorylated by Fyn, in complex with PIK3 reg class 1A and GRB2, resulting in the activation of PI3K [41].

JAK2 also phosphorylates Phospholipase C gamma (PLC-gamma), activating Protein kinase C delta (PKC-delta) via Diacylglycerol (DAG) [2], [42]. PKC-delta phosphorylates and activates STAT3 downstream of Prolactin receptor signaling [43].

The Prolactin receptor dependent interactions of NEK3 with VAV 1 and VAV2 guanine nucleotide exchange factors (VAV1 and VAV2) and Tec with VAV1 regulate cytoskeleton remodeling via activation of small GTPases (Ras homolog gene family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac1)) [10], [11].

References:

  1. Binart N, Ormandy CJ, Kelly PA
    Mammary gland development and the prolactin receptor. Advances in experimental medicine and biology 2000;480:85-92
  2. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA
    Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocrine reviews 1998 Jun;19(3):225-68
  3. Chughtai N, Schimchowitsch S, Lebrun JJ, Ali S
    Prolactin induces SHP-2 association with Stat5, nuclear translocation, and binding to the beta-casein gene promoter in mammary cells. The Journal of biological chemistry 2002 Aug 23;277(34):31107-14
  4. Rozakis-Adcock M, Kelly PA
    Identification of ligand binding determinants of the prolactin receptor. The Journal of biological chemistry 1992 Apr 15;267(11):7428-33
  5. Longhi SA, Cortes MM, Retegui LA
    22- and 20 kDa-human growth hormones bind to different sites within certain cellular receptors. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 2003 Dec;13(6):353-60
  6. Harris J, Stanford PM, Oakes SR, Ormandy CJ
    Prolactin and the prolactin receptor: new targets of an old hormone. Annals of medicine 2004;36(6):414-25
  7. Clevenger CV, Medaglia MV
    The protein tyrosine kinase P59fyn is associated with prolactin (PRL) receptor and is activated by PRL stimulation of T-lymphocytes. Molecular endocrinology (Baltimore, Md.) 1994 Jun;8(6):674-81
  8. Berlanga JJ, Fresno Vara JA, Martin-Perez J, Garcia-Ruiz JP
    Prolactin receptor is associated with c-src kinase in rat liver. Molecular endocrinology (Baltimore, Md.) 1995 Nov;9(11):1461-7
  9. DaSilva L, Rui H, Erwin RA, Howard OM, Kirken RA, Malabarba MG, Hackett RH, Larner AC, Farrar WL
    Prolactin recruits STAT1, STAT3 and STAT5 independent of conserved receptor tyrosines TYR402, TYR479, TYR515 and TYR580. Molecular and cellular endocrinology 1996 Mar 25;117(2):131-40
  10. Kline JB, Moore DJ, Clevenger CV
    Activation and association of the Tec tyrosine kinase with the human prolactin receptor: mapping of a Tec/Vav1-receptor binding site. Molecular endocrinology (Baltimore, Md.) 2001 May;15(5):832-41
  11. Miller SL, DeMaria JE, Freier DO, Riegel AM, Clevenger CV
    Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor. Molecular endocrinology (Baltimore, Md.) 2005 Apr;19(4):939-49
  12. Lee RC, Walters JA, Reyland ME, Anderson SM
    Constitutive activation of the prolactin receptor results in the induction of growth factor-independent proliferation and constitutive activation of signaling molecules. The Journal of biological chemistry 1999 Apr 9;274(15):10024-34
  13. Matsumoto A, Seki Y, Kubo M, Ohtsuka S, Suzuki A, Hayashi I, Tsuji K, Nakahata T, Okabe M, Yamada S, Yoshimura A
    Suppression of STAT5 functions in liver, mammary glands, and T cells in cytokine-inducible SH2-containing protein 1 transgenic mice. Molecular and cellular biology 1999 Sep;19(9):6396-407
  14. Brand JM, Frohn C, Cziupka K, Brockmann C, Kirchner H, Luhm J
    Prolactin triggers pro-inflammatory immune responses in peripheral immune cells. European cytokine network 2004 Apr-Jun;15(2):99-104
  15. Zhu M, John S, Berg M, Leonard WJ
    Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. Cell 1999 Jan 8;96(1):121-30
  16. Sun W, Xu W, Snyder M, He W, Ho H, Ivashkiv LB, Zhang JJ
    The conserved Leu-724 residue is required for both serine phosphorylation and co-activator recruitment for Stat1-mediated transcription activation in response to interferon-gamma. The Journal of biological chemistry 2005 Dec 23;280(51):41844-51
  17. Wyszomierski SL, Rosen JM
    Cooperative effects of STAT5 (signal transducer and activator of transcription 5) and C/EBPbeta (CCAAT/enhancer-binding protein-beta) on beta-casein gene transcription are mediated by the glucocorticoid receptor. Molecular endocrinology (Baltimore, Md.) 2001 Feb;15(2):228-40
  18. Chen Y, Wen R, Yang S, Schuman J, Zhang EE, Yi T, Feng GS, Wang D
    Identification of Shp-2 as a Stat5A phosphatase. The Journal of biological chemistry 2003 May 9;278(19):16520-7
  19. Brockman JL, Schroeder MD, Schuler LA
    PRL activates the cyclin D1 promoter via the Jak2/Stat pathway. Molecular endocrinology (Baltimore, Md.) 2002 Apr;16(4):774-84
  20. Jensen J, Galsgaard ED, Karlsen AE, Lee YC, Nielsen JH
    STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production. The Journal of endocrinology 2005 Oct;187(1):25-36
  21. Wang Y, O'Neal KD, Yu-Lee L
    Multiple prolactin (PRL) receptor cytoplasmic residues and Stat1 mediate PRL signaling to the interferon regulatory factor-1 promoter. Molecular endocrinology (Baltimore, Md.) 1997 Aug;11(9):1353-64
  22. Le Stunff C, Rotwein P
    Growth hormone stimulates interferon regulatory factor-1 gene expression in the liver. Endocrinology 1998 Mar;139(3):859-66
  23. Yu-Lee L
    Stimulation of interferon regulatory factor-1 by prolactin. Lupus 2001;10(10):691-9
  24. Book McAlexander M, Yu-Lee LY
    Sp1 is required for prolactin activation of the interferon regulatory factor-1 gene. Molecular and cellular endocrinology 2001 Nov 26;184(1-2):135-41
  25. Yu-Lee LY
    Prolactin modulation of immune and inflammatory responses. Recent progress in hormone research 2002;57:435-55
  26. Ohmori Y, Schreiber RD, Hamilton TA
    Synergy between interferon-gamma and tumor necrosis factor-alpha in transcriptional activation is mediated by cooperation between signal transducer and activator of transcription 1 and nuclear factor kappaB. The Journal of biological chemistry 1997 Jun 6;272(23):14899-907
  27. Pine R
    Convergence of TNFalpha and IFNgamma signalling pathways through synergistic induction of IRF-1/ISGF-2 is mediated by a composite GAS/kappaB promoter element. Nucleic acids research 1997 Nov 1;25(21):4346-54
  28. Luo G, Yu-Lee L
    Stat5b inhibits NFkappaB-mediated signaling. Molecular endocrinology (Baltimore, Md.) 2000 Jan;14(1):114-23
  29. McAveney KM, Book ML, Ling P, Chebath J, Yu-Lee L
    Association of 2',5'-oligoadenylate synthetase with the prolactin (PRL) receptor: alteration in PRL-inducible stat1 (signal transducer and activator of transcription 1) signaling to the IRF-1 (interferon-regulatory factor 1) promoter. Molecular endocrinology (Baltimore, Md.) 2000 Feb;14(2):295-306
  30. Auernhammer CJ, Bousquet C, Melmed S
    Autoregulation of pituitary corticotroph SOCS-3 expression: characterization of the murine SOCS-3 promoter. Proceedings of the National Academy of Sciences of the United States of America 1999 Jun 8;96(12):6964-9
  31. Tomic S, Chughtai N, Ali S
    SOCS-1, -2, -3: selective targets and functions downstream of the prolactin receptor. Molecular and cellular endocrinology 1999 Dec 20;158(1-2):45-54
  32. Hair WM, Gubbay O, Jabbour HN, Lincoln GA
    Prolactin receptor expression in human testis and accessory tissues: localization and function. Molecular human reproduction 2002 Jul;8(7):606-11
  33. Doan T, Farmer P, Cooney T, Ali MS
    Selective down-regulation of angiotensin II receptor type 1A signaling by protein tyrosine phosphatase SHP-2 in vascular smooth muscle cells. Cellular signalling 2004 Mar;16(3):301-11
  34. Li B, Subleski M, Fusaki N, Yamamoto T, Copeland T, Princler GL, Kung H, Kamata T
    Catalytic activity of the mouse guanine nucleotide exchanger mSOS is activated by Fyn tyrosine protein kinase and the T-cell antigen receptor in T cells. Proceedings of the National Academy of Sciences of the United States of America 1996 Feb 6;93(3):1001-5
  35. Manfroid I, Martial JA, Muller M
    Inhibition of protein phosphatase PP1 in GH3B6, but not in GH3 cells, activates the MEK/ERK/c-fos pathway and the human prolactin promoter, involving the coactivator CPB/p300. Molecular endocrinology (Baltimore, Md.) 2001 Apr;15(4):625-37
  36. Niu S, Xie H, Marcantonio EE
    Integrin-mediated tyrosine phosphorylation of Shc in T cells is regulated by protein kinase C-dependent phosphorylations of Lck. Molecular biology of the cell 2003 Feb;14(2):349-60
  37. Bailey JP, Nieport KM, Herbst MP, Srivastava S, Serra RA, Horseman ND
    Prolactin and transforming growth factor-beta signaling exert opposing effects on mammary gland morphogenesis, involution, and the Akt-forkhead pathway. Molecular endocrinology (Baltimore, Md.) 2004 May;18(5):1171-84
  38. Chakravarti P, Henry MK, Quelle FW
    Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells. International journal of oncology 2005 Feb;26(2):509-14
  39. Chilton BS, Hewetson A
    Prolactin and growth hormone signaling. Current topics in developmental biology 2005;68:1-23
  40. Yamauchi T, Kaburagi Y, Ueki K, Tsuji Y, Stark GR, Kerr IM, Tsushima T, Akanuma Y, Komuro I, Tobe K, Yazaki Y, Kadowaki T
    Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase. The Journal of biological chemistry 1998 Jun 19;273(25):15719-26
  41. Hunter S, Koch BL, Anderson SM
    Phosphorylation of cbl after stimulation of Nb2 cells with prolactin and its association with phosphatidylinositol 3-kinase. Molecular endocrinology (Baltimore, Md.) 1997 Aug;11(9):1213-22
  42. Jackson TA, Schweppe RE, Koterwas DM, Bradford AP
    Fibroblast growth factor activation of the rat PRL promoter is mediated by PKCdelta. Molecular endocrinology (Baltimore, Md.) 2001 Sep;15(9):1517-28
  43. Peters CA, Maizels ET, Robertson MC, Shiu RP, Soloff MS, Hunzicker-Dunn M
    Induction of relaxin messenger RNA expression in response to prolactin receptor activation requires protein kinase C delta signaling. Molecular endocrinology (Baltimore, Md.) 2000 Apr;14(4):576-90

  1. Binart N, Ormandy CJ, Kelly PA
    Mammary gland development and the prolactin receptor. Advances in experimental medicine and biology 2000;480:85-92
  2. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA
    Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocrine reviews 1998 Jun;19(3):225-68
  3. Chughtai N, Schimchowitsch S, Lebrun JJ, Ali S
    Prolactin induces SHP-2 association with Stat5, nuclear translocation, and binding to the beta-casein gene promoter in mammary cells. The Journal of biological chemistry 2002 Aug 23;277(34):31107-14
  4. Rozakis-Adcock M, Kelly PA
    Identification of ligand binding determinants of the prolactin receptor. The Journal of biological chemistry 1992 Apr 15;267(11):7428-33
  5. Longhi SA, Cortes MM, Retegui LA
    22- and 20 kDa-human growth hormones bind to different sites within certain cellular receptors. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 2003 Dec;13(6):353-60
  6. Harris J, Stanford PM, Oakes SR, Ormandy CJ
    Prolactin and the prolactin receptor: new targets of an old hormone. Annals of medicine 2004;36(6):414-25
  7. Clevenger CV, Medaglia MV
    The protein tyrosine kinase P59fyn is associated with prolactin (PRL) receptor and is activated by PRL stimulation of T-lymphocytes. Molecular endocrinology (Baltimore, Md.) 1994 Jun;8(6):674-81
  8. Berlanga JJ, Fresno Vara JA, Martin-Perez J, Garcia-Ruiz JP
    Prolactin receptor is associated with c-src kinase in rat liver. Molecular endocrinology (Baltimore, Md.) 1995 Nov;9(11):1461-7
  9. DaSilva L, Rui H, Erwin RA, Howard OM, Kirken RA, Malabarba MG, Hackett RH, Larner AC, Farrar WL
    Prolactin recruits STAT1, STAT3 and STAT5 independent of conserved receptor tyrosines TYR402, TYR479, TYR515 and TYR580. Molecular and cellular endocrinology 1996 Mar 25;117(2):131-40
  10. Kline JB, Moore DJ, Clevenger CV
    Activation and association of the Tec tyrosine kinase with the human prolactin receptor: mapping of a Tec/Vav1-receptor binding site. Molecular endocrinology (Baltimore, Md.) 2001 May;15(5):832-41
  11. Miller SL, DeMaria JE, Freier DO, Riegel AM, Clevenger CV
    Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor. Molecular endocrinology (Baltimore, Md.) 2005 Apr;19(4):939-49
  12. Lee RC, Walters JA, Reyland ME, Anderson SM
    Constitutive activation of the prolactin receptor results in the induction of growth factor-independent proliferation and constitutive activation of signaling molecules. The Journal of biological chemistry 1999 Apr 9;274(15):10024-34
  13. Matsumoto A, Seki Y, Kubo M, Ohtsuka S, Suzuki A, Hayashi I, Tsuji K, Nakahata T, Okabe M, Yamada S, Yoshimura A
    Suppression of STAT5 functions in liver, mammary glands, and T cells in cytokine-inducible SH2-containing protein 1 transgenic mice. Molecular and cellular biology 1999 Sep;19(9):6396-407
  14. Brand JM, Frohn C, Cziupka K, Brockmann C, Kirchner H, Luhm J
    Prolactin triggers pro-inflammatory immune responses in peripheral immune cells. European cytokine network 2004 Apr-Jun;15(2):99-104
  15. Zhu M, John S, Berg M, Leonard WJ
    Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. Cell 1999 Jan 8;96(1):121-30
  16. Sun W, Xu W, Snyder M, He W, Ho H, Ivashkiv LB, Zhang JJ
    The conserved Leu-724 residue is required for both serine phosphorylation and co-activator recruitment for Stat1-mediated transcription activation in response to interferon-gamma. The Journal of biological chemistry 2005 Dec 23;280(51):41844-51
  17. Wyszomierski SL, Rosen JM
    Cooperative effects of STAT5 (signal transducer and activator of transcription 5) and C/EBPbeta (CCAAT/enhancer-binding protein-beta) on beta-casein gene transcription are mediated by the glucocorticoid receptor. Molecular endocrinology (Baltimore, Md.) 2001 Feb;15(2):228-40
  18. Chen Y, Wen R, Yang S, Schuman J, Zhang EE, Yi T, Feng GS, Wang D
    Identification of Shp-2 as a Stat5A phosphatase. The Journal of biological chemistry 2003 May 9;278(19):16520-7
  19. Brockman JL, Schroeder MD, Schuler LA
    PRL activates the cyclin D1 promoter via the Jak2/Stat pathway. Molecular endocrinology (Baltimore, Md.) 2002 Apr;16(4):774-84
  20. Jensen J, Galsgaard ED, Karlsen AE, Lee YC, Nielsen JH
    STAT5 activation by human GH protects insulin-producing cells against interleukin-1beta, interferon-gamma and tumour necrosis factor-alpha-induced apoptosis independent of nitric oxide production. The Journal of endocrinology 2005 Oct;187(1):25-36
  21. Wang Y, O'Neal KD, Yu-Lee L
    Multiple prolactin (PRL) receptor cytoplasmic residues and Stat1 mediate PRL signaling to the interferon regulatory factor-1 promoter. Molecular endocrinology (Baltimore, Md.) 1997 Aug;11(9):1353-64
  22. Le Stunff C, Rotwein P
    Growth hormone stimulates interferon regulatory factor-1 gene expression in the liver. Endocrinology 1998 Mar;139(3):859-66
  23. Yu-Lee L
    Stimulation of interferon regulatory factor-1 by prolactin. Lupus 2001;10(10):691-9
  24. Book McAlexander M, Yu-Lee LY
    Sp1 is required for prolactin activation of the interferon regulatory factor-1 gene. Molecular and cellular endocrinology 2001 Nov 26;184(1-2):135-41
  25. Yu-Lee LY
    Prolactin modulation of immune and inflammatory responses. Recent progress in hormone research 2002;57:435-55
  26. Ohmori Y, Schreiber RD, Hamilton TA
    Synergy between interferon-gamma and tumor necrosis factor-alpha in transcriptional activation is mediated by cooperation between signal transducer and activator of transcription 1 and nuclear factor kappaB. The Journal of biological chemistry 1997 Jun 6;272(23):14899-907
  27. Pine R
    Convergence of TNFalpha and IFNgamma signalling pathways through synergistic induction of IRF-1/ISGF-2 is mediated by a composite GAS/kappaB promoter element. Nucleic acids research 1997 Nov 1;25(21):4346-54
  28. Luo G, Yu-Lee L
    Stat5b inhibits NFkappaB-mediated signaling. Molecular endocrinology (Baltimore, Md.) 2000 Jan;14(1):114-23
  29. McAveney KM, Book ML, Ling P, Chebath J, Yu-Lee L
    Association of 2',5'-oligoadenylate synthetase with the prolactin (PRL) receptor: alteration in PRL-inducible stat1 (signal transducer and activator of transcription 1) signaling to the IRF-1 (interferon-regulatory factor 1) promoter. Molecular endocrinology (Baltimore, Md.) 2000 Feb;14(2):295-306
  30. Auernhammer CJ, Bousquet C, Melmed S
    Autoregulation of pituitary corticotroph SOCS-3 expression: characterization of the murine SOCS-3 promoter. Proceedings of the National Academy of Sciences of the United States of America 1999 Jun 8;96(12):6964-9
  31. Tomic S, Chughtai N, Ali S
    SOCS-1, -2, -3: selective targets and functions downstream of the prolactin receptor. Molecular and cellular endocrinology 1999 Dec 20;158(1-2):45-54
  32. Hair WM, Gubbay O, Jabbour HN, Lincoln GA
    Prolactin receptor expression in human testis and accessory tissues: localization and function. Molecular human reproduction 2002 Jul;8(7):606-11
  33. Doan T, Farmer P, Cooney T, Ali MS
    Selective down-regulation of angiotensin II receptor type 1A signaling by protein tyrosine phosphatase SHP-2 in vascular smooth muscle cells. Cellular signalling 2004 Mar;16(3):301-11
  34. Li B, Subleski M, Fusaki N, Yamamoto T, Copeland T, Princler GL, Kung H, Kamata T
    Catalytic activity of the mouse guanine nucleotide exchanger mSOS is activated by Fyn tyrosine protein kinase and the T-cell antigen receptor in T cells. Proceedings of the National Academy of Sciences of the United States of America 1996 Feb 6;93(3):1001-5
  35. Manfroid I, Martial JA, Muller M
    Inhibition of protein phosphatase PP1 in GH3B6, but not in GH3 cells, activates the MEK/ERK/c-fos pathway and the human prolactin promoter, involving the coactivator CPB/p300. Molecular endocrinology (Baltimore, Md.) 2001 Apr;15(4):625-37
  36. Niu S, Xie H, Marcantonio EE
    Integrin-mediated tyrosine phosphorylation of Shc in T cells is regulated by protein kinase C-dependent phosphorylations of Lck. Molecular biology of the cell 2003 Feb;14(2):349-60
  37. Bailey JP, Nieport KM, Herbst MP, Srivastava S, Serra RA, Horseman ND
    Prolactin and transforming growth factor-beta signaling exert opposing effects on mammary gland morphogenesis, involution, and the Akt-forkhead pathway. Molecular endocrinology (Baltimore, Md.) 2004 May;18(5):1171-84
  38. Chakravarti P, Henry MK, Quelle FW
    Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells. International journal of oncology 2005 Feb;26(2):509-14
  39. Chilton BS, Hewetson A
    Prolactin and growth hormone signaling. Current topics in developmental biology 2005;68:1-23
  40. Yamauchi T, Kaburagi Y, Ueki K, Tsuji Y, Stark GR, Kerr IM, Tsushima T, Akanuma Y, Komuro I, Tobe K, Yazaki Y, Kadowaki T
    Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase. The Journal of biological chemistry 1998 Jun 19;273(25):15719-26
  41. Hunter S, Koch BL, Anderson SM
    Phosphorylation of cbl after stimulation of Nb2 cells with prolactin and its association with phosphatidylinositol 3-kinase. Molecular endocrinology (Baltimore, Md.) 1997 Aug;11(9):1213-22
  42. Jackson TA, Schweppe RE, Koterwas DM, Bradford AP
    Fibroblast growth factor activation of the rat PRL promoter is mediated by PKCdelta. Molecular endocrinology (Baltimore, Md.) 2001 Sep;15(9):1517-28
  43. Peters CA, Maizels ET, Robertson MC, Shiu RP, Soloff MS, Hunzicker-Dunn M
    Induction of relaxin messenger RNA expression in response to prolactin receptor activation requires protein kinase C delta signaling. Molecular endocrinology (Baltimore, Md.) 2000 Apr;14(4):576-90

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