Dataset Information

Identification of novel LIMK2 phosphorylation substrates

ABSTRACT: Breast cancer is the most common and a lethal form of cancer diagnosed in women worldwide. Although, effective treatment options for primary tumors are available, the majority of breast cancer-related deaths is caused by invasion of cells from primary tumor results in metastatic progression. Here we used a phopshoproteomic analysis to identify new targets of pro-invasive LIM kinase 2 (LIMK2) in invasive breast cancer cell lines. We show that Serine Arginine protein kinase 1 (SRPK1) is phosphorylated and activated by LIMK2 and LIMK2-SRPK1 signaling axis mediate the invasive behavior of breast cancer cells.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: narendra wajapeyee

LAB HEAD: Narendra Wajapeyee

PROVIDER: PXD008246 | Pride | 2020-08-31

REPOSITORIES: Pride

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Publications

LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1.

Malvi Parmanand P Janostiak Radoslav R Chava Suresh S Manrai Padmini P Yoon Esther E Singh Kamaljeet K Harigopal Malini M Gupta Romi R Wajapeyee Narendra N

Oncogenesis 20200828 8

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype and due to the lack of hormone receptors and HER2 expression, TNBC has limited therapeutic options with chemotherapy being the primary choice for systemic therapy. LIM Domain Kinase 2 (LIMK2) is a serine/threonine kinase that plays an important role in the regulation of actin filament dynamics. Here, we show that LIM domain kinase 2 (LIMK2) is overexpressed in TNBC, and short-hairpin RNA (shRNA)-mediated LIMK2 knoc ...[more]

PMID: 32859889

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Project description:Although sex differences in the brain are prevalent, the knowledge about mechanisms underlying sex-related effects on normal and pathological brain functioning is rather poor. It is known that female and male brains differ in size and connectivity. Moreover, those differences are related to neuronal morphology and activity, synapse molecular organization, synaptic plasticity, and molecular signalling pathways. Among different processes assuring proper synapse function are posttranslational modifications, and among them, S-palmitoylation emerges as a crucial mechanism underlying synaptic integrity. Protein S-palmitoylation (S-PALM) refers to the covalent attachment of palmitic acid (C16:0) to cysteine residue(s) via the formation of a thioester bond. Protein S-PALM is governed by a family of PATs, also known as DHHC proteins. Here we focused on the sex-related functional importance of DHHC7 acyltransferase. Under physiological conditions, DHHC7 emerges of particular interest because it palmitoylates various synaptic proteins involved in the regulation of cellular polarity and proliferation as well as in stress and anxiety-related pathology. Moreover, DHHC7 is responsible for S-PALM of sex steroid receptors. Functionally, S-PALM of these receptors regulates their trafficking to the plasma membrane as well as their rapid responses to sex steroid hormones. Using mass spectrometry-based method PANIMoni we identified sex-dependent differences in the S-palmitoylation of synaptic proteins, potentially involved in the regulation of passive membrane properties and excitability (e.g. potassium voltage-gated channels), synaptic transmission (e.g. subunits of glutamate or kainate receptors, voltage-dependent calcium channels) as well as signalling proteins involved in structural plasticity of dendritic spines (e.g. G-proteins and Rab GTPase). Furthermore, to determine a mechanistic source for sex-dependent changes in protein S-palmitoylation we used synaptoneurosomes from DHHC-7 knock-out -/- (DHHC7 KO) female and male mice. Our data showed sex-dependent action of DHHC-7 acyltransferase. Such discovery will facilitate the development of novel and targeted treatments congruous with biological sex.

Dataset Information

Identification of novel LIMK2 phosphorylation substrates

Publications

LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1.

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