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Role of Src Family Kinases in Prolactin Signaling

  • Jorge Martín-PérezEmail author
  • José Manuel García-Martínez
  • María Pilar Sánchez-Bailón
  • Víctor Mayoral-Varo
  • Annarica Calcabrini
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 846)

Abstract

Prolactin (PRL) is a polypeptide hormone/cytokine mainly synthesized by the lactotrophic cells of the adenohypophysis. In addition to the best-known role in mammary gland development and the functional differentiation of its epithelium, PRL is involved in regulation of multiple physiological processes in higher organisms contributing to their homeostasis. PRL has been also associated with pathology, including breast cancer. Therefore, it is relevant to determine the molecular mechanisms by which PRL controls cellular functions. Here, we analyze the role of Src family kinases (SFKs) in the intracellular signaling pathways controlled by PRL in several model systems. The data show that SFKs are essential components in transmitting signals upon PRL receptor stimulation, as they control activation of Jak2/Stat5 and other routes that regulate PRL cellular responses.

Keywords

Conditional Expression Chick Embryo Fibroblast Ferm Domain Jak2 Activation PRLR Isoforms 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

BaF-3 cells

Mouse pro-B lymphocytes

BrdU

5-bromo-2'-deoxyuridine

CEF

Chick embryo fibroblasts

CSK

Carboxyl-terminus Src kinase

EGF

Epidermal growth factor

EGFR, ErbB1

Epidermal growth factor receptor

Erk1/2

Extracellular signal-regulated kinase 1/2

Fak

Focal adhesion kinase

FERM domain

F for 4.1 protein, E for erzin, R for radixin, and M for moesin

FGF

Fibroblast growth factor

FKHRL1, FOXO 3

Forkhead box O3 transcription factor

GH

Growth hormone

Gab2

Grb2-associated-binding protein 2

Grb2

Growth factor receptor-bound protein 2

GSK3ß

Glycogen synthase kinase 3beta

IEG

Immediate early genes

IL-3

Interleukin 3

IGF-IR

Insulin-like growth factor I receptor

IP

Immunoprecipitation

Jak

Janus family kinases

JH

Jak homology domain

Mek1/2

Mitogen-activated protein kinase 1/2

NDF

Neuregulin differentiation factor

PDGF

Platelet-derived growth factor

PRL

Prolactin

PRLR

Prolactin receptor

PI3K

Phosphoinositide 3-kinase

RCAS A or B

Replication-competent avian retroviral vectors derived from RSV

RSV

Rous Sarcoma Virus

SFKs

Src family kinases

SH3

Src homology 3

SH2

Src homology 2

Shp2

Tyrosine phosphatase containing two SH2 domains

Stat

Signal transducers and activators of transcription

WB

Western blot

W53 cells

BaF-3 cells expressing the long form of the PRLR from rat ovary

Notes

Acknowledgments

We would like to thank former members of the group and collaborators for their experimental contributions, P.A. Kelly for his generous gift of PRLR antibody and PRLR cDNA, J.N. Ihle for the Jak2 cDNA, S. Roche and K. Ballmer for c-Src constructs, B.G. Neel and H. Gu for providing BaF-3-rt-Tet cells and Shp2 cDNA constructs, A.F. Parlow (NIDDK) for the supply of oPRL-20, and J Pérez for artwork. The authors acknowledge the support of the SAF2009-09254/SAF2012-38048 grant. We apologize to those colleagues whose work was not recognized.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Jorge Martín-Pérez
    • 1
    Email author
  • José Manuel García-Martínez
    • 1
    • 2
  • María Pilar Sánchez-Bailón
    • 1
  • Víctor Mayoral-Varo
    • 1
  • Annarica Calcabrini
    • 1
    • 3
  1. 1.Department of Cancer BiologyInstituto de Investigaciones Biomédicas A. Sols (CSIC/UAM)MadridSpain
  2. 2.Faculty of Health SciencesUniversidad Rey Juan Carlos IMadridSpain
  3. 3.Department of Technologies and HealthIstituto Superiore di SanitàRomeItaly

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