Dataset Information

Tyrosine phosphorylation of IQGAP1 in the MET pathway

ABSTRACT: Mass spectrometry was used to determine IQGAP1 is a substrate of MET and c-Src, and is phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src cellular activity.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Human

SUBMITTER: Dean McNulty

PROVIDER: MSV000086089 | MassIVE |

SECONDARY ACCESSION(S): PXD021327

REPOSITORIES: MassIVE

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Publications

Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function.

Hedman Andrew C AC McNulty Dean E DE Li Zhigang Z Gorisse Laëtitia L Annan Roland S RS Sacks David B DB

The Journal of biological chemistry 20201021 52

IQGAP1 is a key scaffold protein that regulates numerous cellular processes and signaling pathways. Analogous to many other cellular proteins, IQGAP1 undergoes post-translational modifications, including phosphorylation. Nevertheless, very little is known about the specific sites of phosphorylation or the effects on IQGAP1 function. Here, using several approaches, including MS, site-directed mutagenesis, siRNA-mediated gene silencing, and chemical inhibitors, we identified the specific tyrosine ...[more]

PMID: 33087447

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Project description:Dietary tyrosine regulating melanoma progression has been well-recognized. However, whether tyrosine-based melanin anabolism contributes to pulmonary and cerebral organotropic colonization of melanoma remains elusive. Furthermore, how to inhibit multi-organ metastasis by interfering tyrosinase activity of melanoma cells and function of immunocytes needs to be designed and validated. Patients derived melanoma cells and mouse B16 melanoma cells with different pigment were employed in this investigation. Tyrosine content dynamics in tumors and multiple organs during the melanoma progression were monitored, and tyrosine-based melanin synthesis ability of melanoma cells derived from multi-organ were detected. Additionally, we also adopted the RNA-seq, flowcytometry, real-time PCR and composite metastasis mouse model to analyze organotropic colonization and to design therapeutic strategies. B16 melanoma cells with high activity of tyrosinase and sensitivity of tyrosine utilization for melanin synthesis (Tyr-H cells) easily colonized in the lung, while B16 melanoma cells without above characteristics (Tyr-L cells) exhibited potent proliferation in the brain. Mechanistically, Tyr-H cells recruited and trained neutrophils and macrophages to build up the pulmonary metastatic niche dependent on highly secreted CXCL1 and CXCL2 and an excess melanosome accumulation-induced cell death. Tyr-L cells enhanced PD-L1 expression in tumor-infiltrated macrophages when they are progressing in the brain. Accordingly, intervention of tyrosinase activity (2-Ethoxybenzamide or hydroquinone), together with inhibitors to phagocytosis (GSK343) or chemotaxis (SB225002) suppress organotropic colonization and significantly improve the survival of immune checkpoint blockade (PD1 antibody) treated melanoma bearing mice. The heterogeneity of melanoma cells in utilization of tyrosine is associated with organotropic colonization, providing the basis for developing strategies to combat melanoma and prevent their metastasis.

Dataset Information

Tyrosine phosphorylation of IQGAP1 in the MET pathway

Publications

Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function.

Similar Datasets

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