Cellular Process Interleukin 5 (IL-5) ligand belongs to the cytokine superfamily. IL-5 is a glycoprotein which belongs to the cytokine superfamily. It possesses the four helical bundle motifs that is conserved among several hematopoietic cytokines. IL-5 plays an important role in the proliferation and differentiation of eosinophils. IL-5 induces terminal maturation of eosinophils, prolongs eosinophils survival by delaying apoptotic death, increases eosinophils adhesion to endothelial cells and enhances eosinophils effector function. IL-5 plays important roles in the pathogenesis of asthma, hypereosinophilic syndromes and eosinophil-dependent inflammatory diseases. IL-5 is produced by eosinophils, mast cells, Th2 cells, Tc2 cells and gamma delta T cells. IL-5 exerts influence on different biological activities by associating with the IL-5 receptor. This receptor is a heterodimeric complex consisting of an alpha chain-IL5RA and a beta chain, CSF2RB, which is shared between IL-5 receptor, IL-3 receptor and granulocyte macrophage colony stimulating factor receptor. Binding of IL-5 to the receptor complex results in the recruitment of adapter proteins including SHC1, GRB2 and SOS1. This leads to the activation of the Ras/Raf/MEK/ERK cascade. Subsequent activation of transcription factors including JUN and ELK-1 regulates the expression of genes involved in the control of cell growth and differentiation. IL-5 stimulation also resulted in the activation of PI3K/AKT/RPS6K pathway resulting in the phosphorylation of RPS6 and regulation of gene expression. JAK phosphorylation and activation is also brought about by IL-5, which in turn results in the activation and nuclear translocation of STAT proteins. The STAT transcription factors are responsible for the expression of early response genes and feedback inhibitor of JAK/STAT pathway. In addition, IL-5 is known to activate various tyrosine kinases such as LYN, BTK and SYK. The interactions and intersections between canonical and non-canonical IL-5 signaling systems are depicted in the pathway map. IL-5 stimulation leads to phosphorylation of STAT5B by Jak2 in eosinophils. IL-5 stimulation leads to tyrosine phosphorylation of STAT5A on tyrosine residue 694 in eosinophils. IL-5 stimulation leads to rapid phosphorylation of ERK1 in eosinophils and MC-9 cells. IL-5 stimulation leads to phosphorylation and subsequent activation of AKT1 in eosinophils. IL_5 stimulated the binding of GTP to RAS IL-5 stimulation leads to phosphorylation of JAK2. IL-5 stimulation leads to phosphorylation of JAK1 in COS7 & YY-Bu cells. IL-5 stimulation leads to tyrosine phosphorylation of PTPN11 in human eosinophils. IL-5 stimulation leads to rapid tyrosine phosphorylation of PI3-kinase p85 alpha and beta subunits in Y16 cells. IL-5 stimulation leads to rapid tyrosine phosphorylation of PI3-kinase p85 alpha and beta subunits in Y16 cells. IL-5 stimulation leads to phosphorylation of transcription factor Elk1 in TF-1 cell line. IL-5 stimulation induces autophosphorylation of Btk on tyrosine residue 223 in Y16 cells. IL-5 stimulation leads to phosphorylation of ERK substrate RPS6KA1 in eosinophils. IL-5 stimulation leads to phosphorylation of GSK3-alpha on Serine 21 residue in TF-1 cell line. IL-5 stimulation leads to tyrosine phosphorylation of GSK3-beta on Ser 9 residue in TF-1 cell line. IL-5 stimulation leads to autophosphorylation of p45 MEK in human eosinophils. IL-5 stimulation leads to tyrosine phosphorylation of Shc in Eosinophils, Y16 and FDCP1 cells respectively. IL-5 stimulation leads to tyrosine phosphorylation of c-Jun via the JNK/SAPK pathway in TF-1 cell line. IL-5 stimulation leads to tyrosine phosphorylation of Raf-1 and subsequent activation in human eosinophils. IL-5 stimulation induces tyrosine phosphorylation of the GM-CSF/IL-3/IL-5 receptor beta chain in TF-1 cells. IL-5 stimulation leads to tyrosine phosphorylation of the IL5 receptor alpha subunit in eosinophils. IL-5 stimulation induces ubiquitination on lysine residues 566 and 603 of the GM-CSF/IL-3/IL-5 receptor beta chain in TF-1 cells. IL-5 stimulation leads to phosphorylation at tyrosine 705 of STAT3 in human eosinophils. IL-5 stimulation leads to rapid phosphorylation of ERK2 in eosinophils and MC-9 cells. IL-5 stimulation leads to phosphorylation of FOXO3A on Thr 32 residue in TF-1 cells. IL-5 stimulation leads to tyrosine phosphorylation of STAT1 in eosinophils. IL-5 receptor interacts with cytoplasmic tyrosine kinases like SYK to induce phosphorylation and activation in human eosinophils. IL-5 stimulation leads to binding of JAK2 with the IL5 receptor alpha subunit in eosinophils. IL-5 stimulation leads to activation of constitutively associated JAK1 and GM-CSF/IL-3/IL-5 receptor common beta chain in TF-h5R alpha cells. IL-5 stimulation leads to association of Lyn with IL-5 receptor beta subunit and subsequent phosphorylation in human eosinophils. IL-5 stimulation leads to binding of Lyn with the GM-CSF/IL-3/IL-5 receptor common beta chain in eosinophils. IL-5 stimulation leads to tyrosine phosphorylation of SHP-2 and subsequent association with Grb2 through its SH2 domain in eosinophils. Raf-1 on activation regulates ERKs through activation of MEKs. ERK is a positive regulator of c-fos induction. IL-5 stimulation causes the activation of PI3K in eosinophils. SPRED-1 interacts with RAF-1 and inhibits it in Y-16 cells. Binding of IL-5 to receptor stimulates STAT3 activation.Cytoplasmic proline-rich region of IL-5Rα and the box1 region of the βc subunit are essential for STAT3 activation. IL-5 stimulation induces activation of BTK in Y16 cells. IL-5 stimulation leads to upregulation of PIM-1 through JAK/STAT pathway in eosinophils. IL5 activation induces JAK2 mediated induction of MYC in he IL5 activation induces upregulation of FOS expression through the ras/MAPK pathway in human airway smooth muscle cells. IL5 activation induces JUN expression through the ras/MAPK pathway in human airway smooth muscle cells. IL5 activation induces BCL2 expression in eosinophils. IL-5 stimulation leads to activation and translocation of STAT5A from the cytoplasm to the nucleus in eosinophil- differentiated cell line AML14.3D10. Raf-1 on activation regulates ERKs through activation of MEKs. ERK is a positive regulator of c-fos induction. IL-5 binds to human IL5 receptor alpha subunit with much higher affinity. IL-5 stimulation leads to activation and association of H-Ras with Raf-1 in eosinophils. Activation of RAF induces the phosphorylation and activation of MEKs IL-5 stimulation leads to association of SYK with CSF2RB in eosinophils. IL-5 stimulation leads to autophosphorylation of JAK2 in eosinophils. IL-5 stimulation leads to autophosphorylation of Lyn in eosinophils. Interleukin mediated signaling pathway PW:0000512 Pathway Ontology