Fig. 6
From: Stathmin involvement in the maternal embryonic leucine zipper kinase pathway in glioblastoma
MELK and stathmin signaling. MELK can induce stathmin expression through two transcription factors, p53 and FOXM1. A tyrosine kinase receptor (TKR) is activated by phosphorylation after binding to a ligant. Growth factor receptor-bound protein 2 (GRB2) binds to the phophorylated residue of TKR and to Son of Sevenless homologs (SOS). GRB/SOS complex activates phosphoinositide 3-kinase (PI3K) and RAS-MAPK signaling pathways. Activation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways results in phosphorylation of stathmin on serine sites and consequent microtubule stability and cell cycle progression. Stathmin may be dephosphorylated by protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A) and protein phosphatase 2B (PP2B), resulting in microtubule instability. TKR: tyrosine kinase receptor; P: phosphorylation