IL-3 signaling pathway

Interleukin 3 (IL-3) is a potent growth factor belonging to the super family of cytokines. IL-3 is a 20- 32kDa glycoprotein involved in the process of hematopoiesis. It is involved in the proliferation and differentiation of pleuripotent hematopoietic stem cells, progenitor cells and their mature progeny. IL-3 is a growth factor for B lymphocytes. It also activates monocytes and augments survival and propagation of mast cells, eosinophils and stromal cells. IL-3 is secreted predominantly by activated T lymphocytes in response to immunological stimuli and to a lesser extent by mast cells and eosinophils. IL-3 exerts influence on different biological activities, primarily hematopoiesis by associating with the IL-3 receptor. This receptor is a heterodimeric complex and consists of an alpha chain- IL3RA and a beta chain CSF2RB, shared with the receptors for granulocyte macrophage colony stimulating factor and Interleukin-5. When IL-3 binds to CSF2RB receptor, adapter proteins like SHC1, GRB2 and SOS1 are recruited to activate HRAS. HRAS stimulates RAF1 which further activates MAP2K1 and finally MAPK1 and MAPK3. The signals generated through this pathway are then transmitted to the nucleus leading to the activation of various transcription factors such as JUN and FOS which are involved in the regulation of cell growth and differentiation. IL-3 mediated activation of HRAS also inhibits apoptosis through phosphatidyl inositol 3 kinase/ AKT pathway. The activation of AKT1 in response to IL-3 stimulation leads to the phosphorylation of the apoptotic regulator, BCL2-associated agonist of cell death (BAD), its binding to 14-3-3 and sequestration into the cytoplasm. IL-3 stimulation activates Janus kinase 2 (JAK2) by its phosphorylation. JAK2 in turn phosphorylates signal transducer and activator of transcription 5A and 5B. These translocate to the nucleus, serving the purpose of transcription factor for early genes as well as a feedback inhibitor of the JAK-STAT pathway. IL-3, in addition, is known to activate various tyrosine kinases such as LYN, FYN, SRC, SYK, TEC1 and HCK. The interactions and intersections between canonical and noncanonical IL-3 signaling systems are depicted in the pathway map. Please access this pathway at [http://www.netpath.org/netslim/IL_3_pathway.html NetSlim] database. If you use this pathway, please cite the following paper: Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. <i>Genome Biology</i>. 11:R3.

白介素-3（IL-3）是一种属于细胞因子超家族的强大生长因子。IL-3是一种分子量介于20至32kDa的糖蛋白，参与造血过程。它参与了多能造血干细胞、祖细胞及其成熟后代的增殖和分化。IL-3是B淋巴细胞的生长因子，同时激活单核细胞，增强肥大细胞、嗜酸性粒细胞和基质细胞的存活和增殖。IL-3主要由免疫刺激下被激活的T淋巴细胞分泌，其次由肥大细胞和嗜酸性粒细胞分泌。IL-3通过与其受体结合，影响多种生物学活动，主要通过参与造血。该受体是一种由α链-IL3RA和β链CSF2RB组成的异源二聚体，与粒细胞-巨噬细胞集落刺激因子和白细胞介素-5的受体共享。当IL-3与CSF2RB受体结合时，适配蛋白如SHC1、GRB2和SOS1被招募以激活HRAS。HRAS刺激RAF1，进而激活MAP2K1，最终激活MAPK1和MAPK3。通过此途径产生的信号随后传递至细胞核，导致各种转录因子如JUN和FOS的激活，这些因子参与细胞生长和分化的调控。IL-3介导的HRAS激活还通过磷脂酰肌醇3激酶/ AKT途径抑制细胞凋亡。IL-3刺激导致AKT1的激活，进而磷酸化细胞凋亡调节因子BCL2相关细胞死亡激活剂（BAD），其与14-3-3结合并被隔离到细胞质中。IL-3刺激通过磷酸化激活Janus激酶2（JAK2）。JAK2反过来磷酸化信号转导和转录激活因子5A和5B。这些因子转位到细胞核，作为早期基因的转录因子以及JAK-STAT途径的反馈抑制剂。此外，IL-3还已知激活各种酪氨酸激酶，如LYN、FYN、SRC、SYK、TEC1和HCK。经典和非经典IL-3信号系统之间的相互作用和交叉在通路图中有所描述。请访问[http://www.netpath.org/netslim/IL_3_pathway.html NetSlim]数据库。若使用此通路，请引用以下论文：Kandasamy, K. 等（2010）. NetPath: A public resource of curated signal transduction pathways. <i>Genome Biology</i>. 11:R3.