Networking Between gamma c and GH-R Signaling in the Control of Cell Growth

作者：Romano Rosa; Palamaro Loredana; Parenti Giancarlo; Salerno Mariacarolina; Fusco Anna; Vajro Pietro; Capalbo Donatella; Ranieri Brigida; Naddei Roberta; Pignata Claudio^*

来源：Current Signal Transduction Therapy, 2013, 8(1): 67-73.

DOI：10.2174/1574362411308010009

• Cell growth
• gamma c
• GH
• GH-R
• JAKs
• STATs

The family of type I cytokines, including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, shares common transducing element the common cytokine receptor gamma c. The receptors containing gamma c exert prominent mitogenic effects and play an important role in several immunological functions and in supporting cell survival. The gamma c-dependent cytokine receptors use the Janus Kinase (JAK)/Signal transducer and activator of transcription (STAT) signaling pathway to mediate gene activation or repression. The Growth Hormone (GH) is a peptide of 191 amino acids and 22 kDa molecular weight, produced by the adenohypophysis, that regulates many important functions, as control of cellular metabolism, immune functions, fertility and somatic growth. Of note, the existence of a previously unappreciated functional interaction between gamma c and Growth Hormone receptor (GH-R) has been recently documented. The impairment of various GH-induced events in patients affected with severe combined immunodeficiencies due to gamma c defects suggests a potential functional interaction between GH-R pathways and gamma c, indicating a further link between endocrine and immune system with potential implication of the molecule in the cell cycle progression and control. GH-R pathways and gamma c interaction leads to the activation and intranuclear translocation of STAT5b protein. Moreover, evidence suggests that both GH-induced and spontaneous cell cycle progression and cell growth are strongly dependent on the amount of gamma c expression. To date, the regulation of cell survival and apoptosis can be considered a delicate teamwork and a proper functionality of gamma c-dependent cytokines on the whole seems to play prominent roles, as revealed by the profound impact that their abnormal function can have on the homeostasis of the immune system.

• 出版日期2013-4