ArticleMolecular and cellular biology2001
Nerve growth factor stimulates multisite tyrosine phosphorylation and activation of the atypical protein kinase C's via a src kinase pathway.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 95 citations in OpenAlex.
- Into the fold: advances in understanding aPKC membrane dynamics.The Biochemical journal · 2023Article
- Control of atypical PKCι membrane dissociation by tyrosine phosphorylation within a PB1-C1 interdomain interface.The Journal of biological chemistry · 2023Article
- Proliferative signaling by ERBB proteins and RAF/MEK/ERK effectors in polycystic kidney disease.Cellular signalling · 2020Review
- Experiments with Snails Add to Our Knowledge about the Role of aPKC Subfamily Kinases in Learning.International journal of molecular sciences · 2019Article
- Actin polymerization controls cilia-mediated signaling.The Journal of cell biology · 2018Article
- GGA3 mediates TrkA endocytic recycling to promote sustained Akt phosphorylation and cell survival.Molecular biology of the cell · 2015Article
- Extracellular vesicles shed by glioma cells: pathogenic role and clinical value.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Review
- Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma.Science signaling · 2014Article
- Overexpression of atypical protein kinase C in HeLa cells facilitates macropinocytosis via Src activation.Cellular signalling · 2014Article
- Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids.Carcinogenesis · 2014Article
- Ionizing radiation and glioblastoma exosomes: implications in tumor biology and cell migration.Translational oncology · 2013Article
- NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic mechanisms in colorectal cancer.PLoS genetics · 2013Article
- NNK promotes migration and invasion of lung cancer cells through activation of c-Src/PKCι/FAK loop.Cancer letters · 2012Article
- E3 ubiquitin ligase CHIP facilitates Toll-like receptor signaling by recruiting and polyubiquitinating Src and atypical PKC{zeta}.The Journal of experimental medicine · 2011Article
- Metabolic functions of atypical protein kinase C: "good" and "bad" as defined by nutritional status.American journal of physiology. Endocrinology and metabolism · 2010Review
- Atypical protein kinase C activity is required for extracellular matrix degradation and invasion by Src-transformed cells.Journal of cellular physiology · 2009Article
- Multiple Gi proteins participate in nerve growth factor-induced activation of c-Jun N-terminal kinases in PC12 cells.Neurochemical research · 2009Article
- Structural basis of protein kinase C isoform function.Physiological reviews · 2008Review
- Neurotrophic factors in autonomic nervous system plasticity and dysfunction.Neuromolecular medicine · 2008Review
- A GAPDH mutant defective in Src-dependent tyrosine phosphorylation impedes Rab2-mediated events.Traffic (Copenhagen, Denmark) · 2007Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atypical protein kinase C (PKC) isoforms are required for nerve growth factor (NGF)-initiated differentiation of PC12 cells. In the present study, we report that PKC-iota becomes tyrosine phosphorylated in the membrane coincident with activation posttreatment with nerve growth factor. Tyrosine phosphorylation and activation of PKC-iota were inhibited in a dose-dependent manner by both PP2 and K252a, src and TrkA kinase inhibitors. Purified src was observed to phosphorylate and activate PKC-iota in vitro. In PC12 cells deficient in src kinase activity, both NGF-induced tyrosine phosphorylation and activation of PKC-iota were also diminished. Furthermore, we demonstrate activation of src by NGF along with formation of a signal complex including the TrkA receptor, src, and PKC-iota. Recruitment of PKC-iota into the complex was dependent on the tyrosine phosphorylation state of PKC-iota. The association of src and PKC-iota was constitutive but was enhanced by NGF treatment, with the src homology 3 domain interacting with a PXXP sequence within the regulatory domain of PKC-iota (amino acids 98 to 114). Altogether, these findings support a role for src in regulation of PKC-iota. Tyrosine 256, 271, and 325 were identified as major sites phosphorylated by src in the catalytic domain. Y256F and Y271F mutations did not alter src-induced activation of PKC-iota, whereas the Y325F mutation significantly reduced src-induced activation of PKC-iota. The functional relevance of these mutations was tested by determining the ability of each mutant to support TRAF6 activation of NF-kappaB, with significant impairment by the Y325F PKC-iota mutant. Moreover, when the Y352F mutant was expressed in PC12 cells, NGF's ability to promote survival in serum-free media was reduced. In summary, we have identified a novel mechanism for NGF-induced activation of atypical PKC involving tyrosine phosphorylation by c-Src.
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