Cytokine signaling in tissue engineering

Abstract

Signal transduction is based on the need of different cells to communicate with each other in order to coordinate their growth and differentiation. The mechanisms for such complex regulation include secretion of soluble signaling molecules, as well as direct contacts between cells. Signal transduction pathways usually converge in the nucleus where transcription factors execute distinct gene expression programs. Many, though not all transcription factors bind to a specific base sequence in the promoter region of genes. Signal transducer and activator of transcription (STAT) proteins constitute a family of cytokineinducible transcription factors that modulate broadly diverse biological processes, including cell growth, differentiation, apoptosis, immune regulation, fetal development, and transformation. They were originally discovered as DNA-binding proteins mediating interferon signal transduction. STAT proteins transmit cytokine signals directly from the plasma membrane to the nucleus without the interplay of a second messenger. In response to extracellular ligands receptor-associated Janus kinases (JAKs) activate STATs by phosphorylation on a single tyrosine at the carboxy terminus of the molecule. Activated STAT molecules form dimers through reciprocal interactions between the SH2 domain of one monomer and the phosphorylated tyrosine residue of the other. In the nucleus they bind to sequence-specific DNA elements and modulate the expression of a broad range of target genes. Recently, it was shown that STAT proteins shuttle between the cytoplasm and nucleus both in the presence and absence of cytokine stimulation. In this review we summarize the principles of the JAK-STAT signaling circuit and briefly discuss putative pharmacological interventions thereof used in tissue engineering. © 2009 Springer Berlin Heidelberg.