Protein Kinase C δ (PKCδ) Is Required for Protein Tyrosine Phosphatase μ (PTPμ)-Dependent Neurite Outgrowth

Rosdahl, Jullia A; Mourton, Tracy; Brady‐Kalnay, Susann M.

doi:10.1006/mcne.2001.1071

Cited by 53 publications

(42 citation statements)

References 65 publications

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“…The implications of IQGAP1 binding to nucleotide-depleted Cdc42 are currently unclear. The fact that Ser-1443 enhances neurite outgrowth induced by IQGAP1 is of interest because both PTP-mediated outgrowth and axon guidance of retinal ganglion cells involve the novel PKC, PKC␦ (46,65). We propose that PKC and IQGAP1 are part of a common signaling pathway initiated by PTP homophilic binding.…”

Section: Discussionmentioning

confidence: 99%

The Receptor Protein-tyrosine Phosphatase PTPμ Interacts with IQGAP1

Phillips-Mason

Gates

Major

et al. 2006

Journal of Biological Chemistry

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The receptor protein-tyrosine phosphatase PTP is a member of the Ig superfamily of cell adhesion molecules. The extracellular domain of PTP contains motifs commonly found in cell adhesion molecules. The intracellular domain of PTP contains two conserved catalytic domains, only the membrane-proximal domain has catalytic activity. The unique features of PTP make it an attractive molecule to transduce signals upon cell-cell contact. PTP has been shown to regulate cadherin-mediated cell adhesion, neurite outgrowth, and axon guidance. Protein kinase C is a component of the PTP signaling pathway utilized to regulate these events. To aid in the further characterization of PTP signaling pathways, we used a series of GST-PTP fusion proteins, including catalytically inactive and substrate trapping mutants, to identify PTP-interacting proteins. We identified IQGAP1, a known regulator of the Rho GTPases, Cdc42 and Rac1, as a novel PTP-interacting protein. We show that this interaction is due to direct binding. In addition, we demonstrate that amino acid residues 765-958 of PTP, which include the juxtamembrane domain and 35 residues of the first phosphatase domain, mediate the binding to IQGAP1. Furthermore, we demonstrate that constitutively active Cdc42, and to a lesser extent Rac1, enhances the interaction of PTP and IQGAP1. These data indicate PTP may regulate Rho-GTPase-dependent functions of IQGAP1 and suggest that IQGAP1 is a component of the PTP signaling pathway. In support of this, we show that a peptide that competes IQGAP1 binding to Rho GTPases blocks PTP-mediated neurite outgrowth.Reversible protein-tyrosine phosphorylation is a primary mode of regulation for several cellular functions including growth, differentiation, adhesion, and protein trafficking. The overall tyrosine phosphorylation state of a protein is regulated by protein-tyrosine kinases (1) and protein-tyrosine phosphatases (2). Similar to the family of protein-tyrosine kinases, the family of protein-tyrosine phosphatases includes both non-receptor and receptor type enzymes. Unlike the tyrosine kinases, however, few substrates and downstream signaling molecules of tyrosine phosphatases have been identified. This manuscript focuses on the receptor protein-tyrosine phosphatase (RPTP), 2 PTP, and the identification of novel PTP-interacting proteins to aid in the elucidation of the PTP signaling pathway. The extracellular domain of PTP contains sequence motifs similar to those in cell adhesion molecules including: a MAM domain, an immunoglobulin (Ig) domain, and four fibronectin type-III repeats (3). The MAM domain (Meprins, A5, PTP Mu) is a sequence motif that is suggested to play a role in protein dimerization (4). Ig domains are disulfide-bonded structures found in many cell surface proteins and have been shown to mediate homophilic and heterophilic binding between cell adhesion molecules. Fibronectin type-III motifs, originally identified in the extracellular matrix protein fibronectin, are present in many cell adhesion molecules. PTP has been show...

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Section: Discussionmentioning

confidence: 99%

The Receptor Protein-tyrosine Phosphatase PTPμ Interacts with IQGAP1

Phillips-Mason

Gates

Major

et al. 2006

Journal of Biological Chemistry

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“…Treatment of cells with phorbol esters has little effect on RACK1/PTP association; however, their interaction was found to increase at high cell density, suggesting that it is promoted by cell contact (Mourton et al, 2001). RACK1 and PTP have been shown to exist in a multiprotein complex with PKC␦ in the developing neurites and growth cones of retinal explants (Rosdahl et al, 2002). Blockade of PKC activity with pharmacological inhibitors was found to inhibit outgrowth of neurites on a PTP substrate, providing circumstantial evidence that RACK1 is involved in the regulation of these processes (Rosdahl et al, 2002).…”

Section: Rack1 Signal Transductionmentioning

confidence: 99%

“…RACK1 and PTP have been shown to exist in a multiprotein complex with PKC␦ in the developing neurites and growth cones of retinal explants (Rosdahl et al, 2002). Blockade of PKC activity with pharmacological inhibitors was found to inhibit outgrowth of neurites on a PTP substrate, providing circumstantial evidence that RACK1 is involved in the regulation of these processes (Rosdahl et al, 2002). Indeed, RACK1 is predominantly cytoplasmic in subconfluent cells, but when cell density increases, RACK1 translocates to regions of cell-cell contact to colocalize with PTP (Mourton et al, 2001).…”

Section: Rack1 Signal Transductionmentioning

confidence: 99%

The RACK1 Scaffold Protein: A Dynamic Cog in Cell Response Mechanisms

et al. 2002

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“…PKC-ζ has been localized to photoreceptors (Ghalayini et al, 1994) and -δ possibly to Müller cells (Osborne et al, 1995), but data are conflicting (Ghalayini et al, 1994;Moriarty et al, 2000). PKCδ may affect outgrowth of retinal ganglion cell (RGC) neurites (Rosdahl et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Protein kinase C subtypes and retinal ischemic preconditioning

Dreixler

Shaikh

Shenoy

et al. 2008

Experimental Eye Research

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The purpose of our study was to determine the specific subtypes of protein kinase C involved in the neuroprotection afforded by retinal ischemic preconditioning (IPC), their relationship to the opening of mitochondrial KATP (mKATP) channels, and their role in apoptosis after preconditioning and ischemia. Rats were subjected to retinal ischemia after IPC, or retinas were rendered ischemic after pharmacological opening of mKATP channels. Using immunohistochemistry and image analysis, we determined cellular localization of PKC subtypes. We blocked PKC-δ and -ε to study the effect on protection with IPC or with IPC-mimicking by the opening of mKATP channels. PKC subtypes were inhibited pharmacologically or with interfering RNA. Electroretinography assessed functional recovery after ischemia. IPC was effectively mimicked by injection of diazoxide to open the mKATP channel. IPC and/or its mimicking were attenuated by the PKC-δ inhibitor rottlerin and by interfering RNA targeting PKC-δ or -ε. Using TUNEL staining and Western blotting for caspase-3 and fodrin breakdown we assessed apoptosis. The injection of interfering RNA to PKC-δ and -ε before preconditioning significantly enhanced TUNEL staining as well as the cleavage of caspase-3 and fodrin after ischemia. In summary, our experiments have shown that both PKC-δ and -ε subtypes are involved in the cellular signaling that results in neuroprotection from IPC and that both are downstream of the opening of mKATP channels.

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Protein Kinase C δ (PKCδ) Is Required for Protein Tyrosine Phosphatase μ (PTPμ)-Dependent Neurite Outgrowth

Cited by 53 publications

References 65 publications

The Receptor Protein-tyrosine Phosphatase PTPμ Interacts with IQGAP1

The Receptor Protein-tyrosine Phosphatase PTPμ Interacts with IQGAP1

The RACK1 Scaffold Protein: A Dynamic Cog in Cell Response Mechanisms

Protein kinase C subtypes and retinal ischemic preconditioning

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