Premium
A Reevaluation of the Role of Phosphatidylinositol Transfer Protein a in Growth Factor Signaling
Author(s) -
McDermott Mark I.,
Diz Ramiro,
Hur Seong,
Lete Marta G.,
Applebee Christopher J.,
Grabon Aby,
Tripathi Ashutosh,
Wakelam Michael J. O.,
Larijani Banafshe,
Bankaitis Vytas A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.540.5
Subject(s) - biology , microbiology and biotechnology , signal transduction , protein kinase b , phosphorylation , epidermal growth factor , netrin , proto oncogene proteins c akt , pi3k/akt/mtor pathway , autocrine signalling , axon guidance , receptor , genetics , axon
Despite current dogma stating that phosphatidylinositol transfer protein a (PITPa) is required for growth factor signaling, little evidence has emerged supporting these claims. Data from our laboratory, gathered from multiple experimental systems, strongly dispute the current doctrine and indicate that in contrast to previous reports PITPa is dispensable for epidermal growth factor (EGF), and netrin signaling. Mouse and human cell lines lacking PITPa sense and chemotax towards EGF. Furthermore, signaling responses in these lines, including phosphatidylinositol (3,4,5)P 3 generation and phosphorylation of protein kinase B (Akt), downstream of EGF‐receptor (EGFR) stimulation are unimpaired. Surprisingly, human cells lacking PITPa displayed elevated Akt (Thr308) phosphorylation following EGF‐stimulation, indicating that not only is PITPa dispensable for Akt phosphorylation, but contrary to current thinking it may actually repress this pathway. PITPa dispensability for EGF‐signaling explains the striking absence of EGF‐signaling related phenotypes in PITPa nullizygous mice. We have previously reported that these animals display a complex phenotype including spinocerebellar neurodegeneration characterized by neuronal apoptosis and gliosis of cerebellum, and hindbrain. Netrin signaling through the netrin receptor (DCC) is required for axon guidance and mouse forebrain development, and is reported to require PITPa. We demonstrate that absence of PITPa does not result in structural brain derangements associated with compromise of netrin‐signaling. Moreover, the previously reported interaction between the netrin receptor (DCC) and PITPa could not be reproduced. Clearly the ‘essential’ role of PITPa in growth factor signaling must be reevaluated. Support or Funding Information This research was funded by NIH grant R01‐GM112591 and grant BE‐0017 from the Robert A. Welch Foundation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .