Region‐specific mRNA expression of phosphatidylinositol 3‐kinase regulatory isoforms in the central nervous system of C57BL/6J mice

D Hörsch, CR Kahn - Journal of Comparative Neurology, 1999 - Wiley Online Library
D Hörsch, CR Kahn
Journal of Comparative Neurology, 1999Wiley Online Library
Activation of phosphatidylinositol 3‐kinase (PI 3‐kinase) by receptor tyrosine kinases for
growth factors is crucial for neuronal cell survival and proliferation. This class of kinases is
comprised of heterodimers, each consisting of one regulatory and one catalytic subunit.
Multiple isoforms of regulatory subunits exist, including p85α and its alternative splice
products p50α and AS53/p55α, and p85β and p55PIK, which are derived from different
genes. The regional distribution of these PI 3‐kinase regulatory isoforms was mapped in the …
Abstract
Activation of phosphatidylinositol 3‐kinase (PI 3‐kinase) by receptor tyrosine kinases for growth factors is crucial for neuronal cell survival and proliferation. This class of kinases is comprised of heterodimers, each consisting of one regulatory and one catalytic subunit. Multiple isoforms of regulatory subunits exist, including p85α and its alternative splice products p50α and AS53/p55α, and p85β and p55PIK, which are derived from different genes. The regional distribution of these PI 3‐kinase regulatory isoforms was mapped in the adult murine brain by in situ hybridization histochemistry. All isoforms were demonstrated in abundance in choroid plexus and anterior pituitary. In neuronal compartments, however, PI 3‐kinase isoforms were distributed in a regionally specific manner. In general, the mRNAs for p85α, p50α, AS53, and p85β were widespread, with the highest level in the olfactory system, in neuronal groups of the forebrain and hypothalamus, in the hippocampus, cortex, inferior and superior colliculus, pituitary, and cerebellum. However, each isoform had specific variations. Lower expression levels of these isoforms were found in the thalamus, diencephalon, mesencephalon, and brainstem. In contrast, abundant mRNA expression of p55PIK was limited to cerebellum and anterior pituitary, with moderate levels of p55PIK in the olfactory bulb and hippocampus and low levels elsewhere. The distribution pattern of PI 3‐kinase isoforms in the brain indicates pluripotent signaling properties for PI 3‐kinase isoforms p85α, p50α, AS53/p55α, and p85β for a variety of receptor tyrosine kinases, whereas the restricted expression of p55PIK implies a regionally specific role for this isoform in neuronal signaling. The unique integrated expression profiles of PI 3‐kinase isoforms in distinct neuronal compartments denote complex intracellular signaling pathways for each neuronal region to ensure specificity of receptor tyrosine kinase signal transduction. J. Comp. Neurol. 415:105–120, 1999. © 1999 Wiley‐Liss, Inc.
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