To Contribution To Hematopoietic Cell Development And The Mammalian Cell

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The ability to respond to external signaling is an inherent property of all mammalian cells. External stimuli could be in the form of hormones or mitogens and can lead to further intracellular signaling pathways that trigger cellular changes. This internal mechanism of communication is essential to the development of an organism and plays a critical role in growth, homeostasis and cellular defense system. Among the various pathways that regulate cellular functions, JAK/STAT pathway is one that allows communication between membrane receptors and the nucleus. Extensive studies of this pathway have led us to understand gene expression via nuclear signaling. JAK/STAT significantly contributes to hematopoietic cell development and
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Once STAT has been phosphorylated it can recruit other STAT units to itself forming homodimers or heterodimers. Dimerization of STAT proteins allows the homodimer/heterodimer to be translocated to the nucleus where it then binds to gamma activated sequence (GAS) elements within the nucleus. Binding of STAT proteins to GAS elements in the DNA leads to the transcription of target genes which ultimately play a crucial role in cellular viability, survival, apoptosis, etc. (1,2) Activation of the JAK/STAT pathway is responsible for initiation of multiple signal transduction cascades such as Ras-Raf-MEK-Erk, PI3K-Akt-mTOR and phospholipase C-γ.
Excessive stimulation of cytokine regulated cascades is seldom unaccompanied by adverse events. Negative regulation as such is accomplished by protein tyrosine phosphatases (e.g. SHP-1, CD45) which act by removing phosphates from phosphorylated proteins, suppressor of cytokine signaling proteins (SOCS) that competitively inhibit STAT phosphorylation by binding or inhibiting JAKs and the protein inhibitors of STATs (PIAS) which block the binding sites of STATs in the DNA thereby inhibiting the transcriptional activation (3).
Implications of JAK-STAT in disease
So far, we have seen that this pathway is accountable for the transduction of extracellular stimulus into transcriptional factors that regulate several cellular functions.

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