The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3

Cordon‐Cardo, Carlos; Tapley, Peter; Jing, Shuqian; Nanduri, Venkata; O'Rourke, Edward; Lamballe, Fabienne; Kovary, K; Klein, Rüdiger; Jones, Kevin R.; Reichardt, Louis F.; Barbacid, Mariano

doi:10.1016/0092-8674(91)90149-s

Cited by 496 publications

(228 citation statements)

References 66 publications

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“…Indeed, PTPlc and PTP/2 were shown to mediate homophilic cell adhesion when expressed in insect cells using recombinant baculovirus expression systems [17][18][19] It is well known that several PTKs, such as the src-family of PTKs, are abundantly expressed in the central nervous systemm [20][21][22][23] and the immune system (reviewed in [3]). The receptors for nerve growth factor and several neurotropic factors have intrinsic PTK activity [24][25][26][27]. In the immune system, soluble-form PTKs have been shown to be associated with antigen receptors (reviewed in [3]) and growth factor receptors [28].…”

Section: Introductionmentioning

confidence: 99%

Developmental regulation of gene expression for the MPTPδ isoforms in the central nervous system and the immune system

Mizuno¹,

Hasegawa²,

Ogimoto³

et al. 1994

FEBS Letters

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MPTP6 is a murine transmembrane protein tyrosine phosphatase which has three isoforms, types A-C, differing in the structure of the extracellular regions. In this study, we examined MPTP~ isoform expression in the brain and the immune system at discrete developmental or differentiation stages. RT-PCR analysis demonstrated that another isoform, type D, is transcribed from the MPTP~ gene. In\the brain, only type D was expressed until postnatal day 7 (P7), but after P14, all four isoforms were detected. In contrast, the spleen, thymus and all the hematopoietic cell lines examined express only types B and C isoforms. An in situ hybridization study showed that MPTP6 mRNA is diffusely expressed throughout the spleen, but its expression in the thymus is restricted to the medullary region.

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Section: Introductionmentioning

confidence: 99%

Developmental regulation of gene expression for the MPTPδ isoforms in the central nervous system and the immune system

Mizuno¹,

Hasegawa²,

Ogimoto³

et al. 1994

FEBS Letters

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“…Binding of cognate NTFs to their corresponding trk receptors ectopically expressed in fibroblasts induces autophosphorylation of the receptors and transduces the signals. Thus, trkA is a functional receptor for NGF (Klein et al, 1991b;Cordon-Cardo et al, 1991;Jing et al, 1992;Ip et al, 1993), trkB can be functionally activated by both BDNF (Klein et al, 1991a;Squinto et al, 1991;Glass et al, 1991;Ip et al, 1993) and NT-4 (Klein et al, 1992;Ip et al, 1993), whereas NT-3 is a ~nonpreferred ~ ligand for trkB Klein et al, 1991a;Squinto et al, 1991;Ip et al, 1993). trkC serves as a functional receptor for NT-3 (Lamballe et al, 1991;Ip et al, 1993).…”

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confidence: 99%

Neurotrophins and their receptors in rat peripheral trigeminal system during maxillary nerve growth

Arumäe

Pirvola

Palgi

et al. 1993

The Journal of Cell Biology

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Abstract. We examined the expression of the neurotrophins (NTFs) and their receptor mRNAs in the rat trigeminal ganglion and the first branchial arch before and at the time of maxillary nerve growth. The maxillary nerve appears first at embryonic day (E)10 and reaches the epithelium of the first branchial arch at El2, as revealed by anti-L1 immunohistochemistry. In situ hybridization demonstrates, that at E10-Ell, neurotrophin-3 (NT-3) mRNA is expressed mainly in the mesenchyme, but neurotrophin-4 (NT-4) mRNA in the epithelium of the first branchial arch. NGF and brain-derived neurotrophic factor (BDNF) mRNAs start to be expressed in the distal part of the first branchial arch shortly before its innervation by the maxillary nerve. Trigeminal ganglia strongly express the mRNA of trkA at El0 and thereafter. The expression of mRNAs for low-affinity neurotrophin receptor (LANR), trkB, and trkC in trigeminal ganglia is weak at El0, but increases by Ell-E12. NT-3, NT-4, and more prominently BDNF, induce neurite outgrowth from explant cultures of the El0 trigeminal ganglia but no neurites are induced by NGF, despite the expression of trkA. By E12, the neuritogenic potency of NGF also appears. The expression of NT-3 and NT-4 and their receptors in the trigeminal system prior to target field innervation suggests that these NTFs have also other functions than being the target-derived trophic factors.

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“…The transfection efficiency, deduced from the frequency of G418-resistant colonies, was similar for all the constructs (data not shown). As previously shown (Cordon-Cardo et al, 1991), the wild type receptor produced foci only in the presence of NGF. No foci were detected in cells transfected with the M688T mutant NTRK1 (Figure 3a,b), either in the absence or in the presence of NGF.…”

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confidence: 62%

Gain of function mutations of RTK conserved residues display differential effects on NTRK1 kinase activity

et al. 2002

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Activation of tyrosine kinase receptors is associated with human tumors. Tumorigenic versions of several RTKs, such as Ret, Kit and Met carry activating mutations at highly conserved residues of the tyrosine kinase domain. We have investigated the effect of some of these mutations on the NTRK1/NGF receptor, for which no naturally occurring activating point mutations have been so far detected. We introduced the following mutations in NTRK1 tyrosine kinase domain: (i) D668N equivalent to Met D1246N associated to HPRC; (ii) D668V modelled on Kit D816V found in mastocytosis; (iii) M688T corresponding to Ret M918T associated to the cancer syndrome MEN2B. The Met-like mutation rendered the NTRK1 receptor more responsive to ligand, as observed for the corresponding mutation in Met. On the contrary the Kit-like D668V resulted as neutral mutation. Surprisingly, the MEN2B-like M688T completely abrogated NTRK1 receptor activity, resulting as a loss of function mutation. Our results show that the mutations tested, although involving conserved amino acids in highly homologous regions, exert distinct effects in different receptors, and suggest a very peculiar autoinhibitory mechanism for NTRK1.

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The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3

Cited by 496 publications

References 66 publications

Developmental regulation of gene expression for the MPTPδ isoforms in the central nervous system and the immune system

Developmental regulation of gene expression for the MPTPδ isoforms in the central nervous system and the immune system

Neurotrophins and their receptors in rat peripheral trigeminal system during maxillary nerve growth

Gain of function mutations of RTK conserved residues display differential effects on NTRK1 kinase activity

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