Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor I receptor (IGF-IR) has been implicated in the normal and malignant growth of many cell types including cells from the central nervous system. In the cerebellar cortex IGF-IR mRNA is found in granular cells and IGF-I stimulation is mitogenic and protects cells from low-potassium-induced apoptosis. Since primitive neuroectodermal tumors/medulloblastomas (PNETs/medulloblastomas) are suspected to originate from the external cerebellar granular layer, it is reasonable to postulate that IGF-IR and/or its signaling molecules may contribute to the transformation of these poorly differentiated cells. To study activation of the IGF-IR system in medulloblastomas, we have utilized an antibody (anti-pY1316) that specifically recognizes the phosphorylated (active) form of the IGF-IR. Medulloblastoma biopsy specimens were positive when examined immunohistochemically with anti-Y1316 antibody. Further analysis of the IGF-IR system was performed in three human (Daoy, TE-671, D283 Med) and four mouse (BsB8, BsB13, Bs-1b, Bs-1c) medulloblastoma cell lines. All the murine cell lines examined express IGF-IR and PI3-kinase at relatively normal levels, and grossly overexpress IRS-1, when compared with normal mouse cerebellum. Within 15 min following IGF-I stimulation both mouse and human cell lines phosphorylate the beta subunit of the IGF-IR, IRS-1, Akt, and MAP kinases. They respond with cell proliferation when stimulated solely with IGF-I and are strongly inhibited when challenged with a dominant negative mutant of the IGF-IR (486/STOP), or with antisense oligonucleotides against the IGF-IR mRNA.
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PMID:Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas. 1143 49

Mitogen-activated protein kinase and Phosphatidylinositol-3 kinase/Akt-mediated signaling pathways play a major role in controlling cell proliferation, differentiation and cell death. Phosphorylation and dephosphorylation of their specific Thr/Tyr residues is critical in determining their activity. We determined the expression pattern and activity of MAP kinases and Akt in Primitive Neuroectodermal Tumors (PNETs). The kinase activity of extracellular signal-regulated kinase (ERK) was higher in both primary tumors and cell lines, as evident from the increased phosphorylation of ERK1 and ERK2. We did not observe the activation of C-jun N-terminal kinase (JNK) or p38 MAPK The expression of Raf-1, a kinase acting upstream of ERK, was significantly increased in primary tumors compared to normal brain. The PI-3 kinase-activated phosphorylation of Akt was also higher in primary tumors. These results suggest that activation of the Raf-1/ERK module of the MAP kinase pathway play an important role in PNETs.
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PMID:Role of MAP kinase pathways in primitive neuroectodermal tumors. 1172 48