Title:Networking Between γc and GH-R Signaling in the Control of Cell Growth
VOLUME: 8 ISSUE: 1
Author(s):Rosa Romano, Loredana Palamaro, Giancarlo Parenti, Mariacarolina Salerno, Anna Fusco, Pietro Vajro, Donatella Capalbo, Brigida Ranieri, Roberta Naddei and Claudio Pignata
Affiliation:Department of Pediatrics, "Federico II" University, Naples, via S. Pansini 5 - 80131, Italy.
Keywords:Cell growth, γc, GH, GH-R, JAKs, STATs, Cytokines, Combined Immunod eficiency (X-SCID)
Abstract: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 γc. The receptors containing γc exert prominent mitogenic effects and play an
important role in several immunological functions and in supporting cell survival. The γc-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 γc and Growth Hormone receptor (GH-R) has been recently documented. The impairment of various GHinduced
events in patients affected with severe combined immunodeficiencies due to γc defects suggests a potential
functional interaction between GH-R pathways and γc, 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 γc interaction
leads to the activation and intranuclear translocation of STAT5b protein. Moreover, evidence suggests that both GHinduced
and spontaneous cell cycle progression and cell growth are strongly dependent on the amount of γc expression.
To date, the regulation of cell survival and apoptosis can be considered a delicate teamwork and a proper functionality of
γc-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.
