PMID- 11257612 OWN - NLM STAT- MEDLINE DCOM- 20010531 LR - 20191104 IS - 0022-3034 (Print) IS - 0022-3034 (Linking) VI - 47 IP - 1 DP - 2001 Apr TI - Phosphatidylinositol-3-OH kinase regulatory subunits are differentially expressed during development of the rat cerebellum. PG - 39-50 AB - Recent evidence implicates a central role for PI3K signalling in mediating cell survival during the process of neuronal differentiation. Although PI3K activity is stimulated by a wide range of growth factors and cytokines in different cell lines and tissues, activation of this pathway by insulin-like growth factor I (IGF-I) most likely represents the main survival signal during neuronal differentiation. IGF-I is highly expressed during development of the central nervous system, and thus is a critical factor for the development and maturation of the cerebellum. Upon ligand binding, the IGF-I receptor phosphorylates tyrosine residues in SHC and insulin receptor substrates (IRSs) initiating two main signalling cascades, the MAP kinase and the phosphatidylinositol 3-kinase (PI3K) pathways. Activated PI3K is composed of a catalytic subunit (p110alpha or beta) associated with one of a large family of regulatory subunits (p85alpha, p85beta, p55gamma, p55alpha, and p50alpha). To evaluate the contributions of these various regulatory subunits to neuronal differentiation, we have used antibodies specific for each of the PI3K subunits. Using these antisera, we now demonstrate that PI3K subunits are differentially regulated in cerebellar development, and that the expression level of the p55gamma regulatory subunit reaches a maximum during postnatal development, decreasing thereafter to low levels in the adult cerebellum. Furthermore, our studies reveal that the distribution of the various PI3K regulatory subunits varies during development of the cerebellum. Interestingly, p55gamma is expressed in both glial and neuronal cells; moreover, in Purkinje neurones, this subunit colocalises with the IGF-IR. CI - Copyright 2001 John Wiley & Sons, Inc. FAU - Trejo, J L AU - Trejo JL AD - Cellular and Molecular Neuroendocrinology Laboratory, Instituto Cajal de Neurobiologia, C.S.I.C., Av. Doctor Arce 37, Madrid E28002, Spain. FAU - Pons, S AU - Pons S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurobiol JT - Journal of neurobiology JID - 0213640 RN - 0 (Protein Subunits) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Receptor, IGF Type 1) SB - IM MH - Animals MH - Antibody Specificity MH - Blotting, Western MH - COS Cells MH - Cerebellum/*enzymology/*growth & development MH - Gene Expression Regulation, Developmental MH - Immunohistochemistry MH - Neuroglia/cytology/metabolism MH - Neurons/cytology/metabolism MH - Phosphatidylinositol 3-Kinases/*biosynthesis/genetics MH - *Protein Subunits MH - Purkinje Cells/cytology/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, IGF Type 1/metabolism EDAT- 2001/03/21 10:00 MHDA- 2001/06/02 10:01 CRDT- 2001/03/21 10:00 PHST- 2001/03/21 10:00 [pubmed] PHST- 2001/06/02 10:01 [medline] PHST- 2001/03/21 10:00 [entrez] AID - 10.1002/neu.1014 [pii] AID - 10.1002/neu.1014 [doi] PST - ppublish SO - J Neurobiol. 2001 Apr;47(1):39-50. doi: 10.1002/neu.1014.