TAM Signaling in the Nervous System

Tyro3, Axl and Mertk are members of the TAM family of tyrosine kinase receptors. TAMs are activated by two structurally homologous ligands GAS6 and PROS1. TAM receptors and ligands are widely distributed and often co-expressed in the same cells allowing diverse functions across many systems including the immune, reproductive, vascular, and the developing and adult nervous systems. This review will focus specifically on TAM signaling in the nervous system, highlighting the essential roles they play in maintaining cell survival and homeostasis, cellular functions such as phagocytosis, immunity and tissue repair. Dysfunctional TAM signaling can cause complications in development, disruptions in homeostasis which can rouse autoimmunity, neuroinflammation and neurodegeneration. The development of therapeutics modulating TAM activities in the nervous system has great prospects, however, foremost we need a complete understanding of TAM signaling pathways.

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Erbb transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system

The Journal of Comparative Neurology ◽

10.1002/cne.1127 ◽

2001 ◽

Vol 433 (1) ◽

pp. 86-100 ◽

Cited By ~ 95

Author(s):

Kimberly M. Gerecke ◽

J. Michael Wyss ◽

Irina Karavanova ◽

Andres Buonanno ◽

Steven L. Carroll

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tyrosine Kinase ◽

Differentially Expressed ◽

Tyrosine Kinase Receptors ◽

Adult Rat

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Mechanisms of Murine Mammary Tumorigenesis: Cooperation Between Tyrosine Kinase Receptors and Mutant p53.

10.21236/ada335188 ◽

1997 ◽

Author(s):

Archibald Perkins

Keyword(s):

Tyrosine Kinase ◽

Mammary Tumorigenesis ◽

Tyrosine Kinase Receptors ◽

Mutant P53

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Radiolabeled Probes Targeting Tyrosine-Kinase Receptors For Personalized Medicine

Current Pharmaceutical Design ◽

10.2174/13816128113196660667 ◽

2014 ◽

Vol 20 (14) ◽

pp. 2275-2292 ◽

Cited By ~ 11

Author(s):

Mohamed Altai ◽

Anna Orlova ◽

Vladimir Tolmachev

Keyword(s):

Personalized Medicine ◽

Tyrosine Kinase ◽

Tyrosine Kinase Receptors

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Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

Current Stem Cell Research & Therapy ◽

10.2174/1574888x13666180723104340 ◽

2019 ◽

Vol 14 (3) ◽

pp. 219-225 ◽

Cited By ~ 6

Author(s):

Cong Tang ◽

Guodong Zhu

Keyword(s):

Cancer Therapy ◽

Tyrosine Kinase ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Cell Receptor ◽

Transmembrane Receptors ◽

Biological Responses ◽

Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

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Tyrosine Kinase Signaling Pathways Modulate Angiotensin II–Induced Calcium ([Ca2+]i) Transients in Vascular Smooth Muscle Cells

Hypertension ◽

10.1161/01.hyp.27.5.1097 ◽

1996 ◽

Vol 27 (5) ◽

pp. 1097-1103 ◽

Cited By ~ 29

Author(s):

R.M. Touyz ◽

E.L. Schiffrin

Keyword(s):

Smooth Muscle ◽

Angiotensin Ii ◽

Vascular Smooth Muscle ◽

Tyrosine Kinase ◽

Smooth Muscle Cells ◽

Signaling Pathways ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Kinase Signaling ◽

Tyrosine Kinase Signaling

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Revising Endosomal Trafficking under Insulin Receptor Activation

International Journal of Molecular Sciences ◽

10.3390/ijms22136978 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6978

Author(s):

Maria J. Iraburu ◽

Tommy Garner ◽

Cristina Montiel-Duarte

Keyword(s):

Plasma Membrane ◽

Tyrosine Kinase ◽

Insulin Receptor ◽

Molecular Mechanisms ◽

Receptor Activation ◽

Small Gtpases ◽

Early Endosome ◽

Tyrosine Kinase Receptors ◽

Endosomal Trafficking ◽

Cell Functions

The endocytosis of ligand-bound receptors and their eventual recycling to the plasma membrane (PM) are processes that have an influence on signalling activity and therefore on many cell functions, including migration and proliferation. Like other tyrosine kinase receptors (TKR), the insulin receptor (INSR) has been shown to be endocytosed by clathrin-dependent and -independent mechanisms. Once at the early endosome (EE), the sorting of the receptor, either to the late endosome (LE) for degradation or back to the PM through slow or fast recycling pathways, will determine the intensity and duration of insulin effects. Both the endocytic and the endosomic pathways are regulated by many proteins, the Arf and Rab families of small GTPases being some of the most relevant. Here, we argue for a specific role for the slow recycling route, whilst we review the main molecular mechanisms involved in INSR endocytosis, sorting and recycling, as well as their possible role in cell functions.

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Spleen tyrosine kinase regulates crosstalk of hypoxia-inducible factor-1α and nuclear factor (erythroid-derived2)-like 2 for B cell survival

International Immunopharmacology ◽

10.1016/j.intimp.2021.107509 ◽

2021 ◽

Vol 95 ◽

pp. 107509

Author(s):

Ju-Won Jang ◽

Sojin Park ◽

Eun-Yi Moon

Keyword(s):

Tyrosine Kinase ◽

B Cell ◽

Cell Survival ◽

Hypoxia Inducible Factor ◽

Nuclear Factor ◽

Spleen Tyrosine Kinase ◽

Hypoxia Inducible Factor 1Α ◽

B Cell Survival

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Epigallocatechin gallate protects the human lens epithelial cell survival against UVB irradiation through AIF/Endo G signaling pathways in vitro

Cutaneous and Ocular Toxicology ◽

10.1080/15569527.2021.1879112 ◽

2021 ◽

pp. 1-25

Author(s):

Qiuxin Wu ◽

Zhongen Li ◽

Xiuzhen Lu ◽

Jike Song ◽

Hui Wang ◽

...

Keyword(s):

Epithelial Cell ◽

Cell Survival ◽

Signaling Pathways ◽

Epigallocatechin Gallate ◽

Lens Epithelial Cell ◽

Human Lens ◽

Uvb Irradiation ◽

Human Lens Epithelial Cell

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Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections.

The Journal of Cell Biology ◽

10.1083/jcb.96.5.1337 ◽

1983 ◽

Vol 96 (5) ◽

pp. 1337-1354 ◽

Cited By ~ 345

Author(s):

P De Camilli ◽

R Cameron ◽

P Greengard

Keyword(s):

Nervous System ◽

Detailed Examination ◽

Specific Protein ◽

Nerve Cells ◽

General Distribution ◽

Synapsin I ◽

Nervous Systems ◽

Synaptic Region ◽

Specific Localization ◽

Peripheral Nervous Systems

Synapsin I (formerly referred to as protein I) is the collective name for two almost identical phosphoproteins, synapsin Ia and synapsin Ib (protein Ia and protein Ib), present in the nervous system. Synapsin I has previously been shown by immunoperoxidase studies (De Camilli, P., T. Ueda, F. E. Bloom, E. Battenberg, and P. Greengard, 1979, Proc. Natl. Acad. Sci. USA, 76:5977-5981; Bloom, F. E., T. Ueda, E. Battenberg, and P. Greengard, 1979, Proc. Natl. Acad. Sci. USA 76:5982-5986) to be a neuron-specific protein, present in both the central and peripheral nervous systems and concentrated in the synaptic region of nerve cells. In those preliminary studies, the occurrence of synapsin I could be demonstrated in only a portion of synapses. We have now carried out a detailed examination of the distribution of synapsin I immunoreactivity in the central and peripheral nervous systems. In this study we have attempted to maximize the level of resolution of immunohistochemical light microscopy images in order to estimate the proportion of immunoreactive synapses and to establish their precise distribution. Optimal results were obtained by the use of immunofluorescence in semithin sections (approximately 1 micron) prepared from Epon-embedded nonosmicated tissues after the Epon had been removed. Our results confirm the previous observations on the specific localization of synapsin I in nerve cells and synapses. In addition, the results strongly suggest that, with a few possible exceptions involving highly specialized neurons, all synapses contain synapsin I. Finally, immunocytochemical experiments indicate that synapsin I appearance in the various regions of the developing nervous system correlates topographically and temporally with the appearance of synapses. In two accompanying papers (De Camilli, P., S. M. Harris, Jr., W. B. Huttner, and P. Greengard, and Huttner, W. B., W. Schiebler, P. Greengard, and P. De Camilli, 1983, J. Cell Biol. 96:1355-1373 and 1374-1388, respectively), evidence is presented that synapsin I is specifically associated with synaptic vesicles in nerve endings.

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