trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development.

Abstract

We have isolated a novel member of the tyrosine protein kinase family of cell surface receptors. This gene, designated trkB, is highly related to the human trk proto‐oncogene. At the amino acid level, their respective products share a 57% homology in their extracellular regions including 9 of the 11 cysteines present in the trk proto‐oncogene. This homology increases to 88% within their respective tyrosine kinase catalytic domains. Both trk and trkB are equally distantly related to the other members of this gene family of receptors. A biologically active cDNA clone of trkB can direct the synthesis of gp145trkB, a glycoprotein of 145 kd of which only 93 kd correspond to its polypeptide backbone. In adult mice, trkB is preferentially expressed in brain tissue, although significant levels of trkB RNA have also been observed in lung, muscle and ovaries. In addition, trkB transcripts can be detected in mid and late gestation embryos. The trkB locus exhibits a complex pattern of transcription. At least seven RNA species ranging in size from approximately 9 kb to 2 kb have been identified in brain. However, only a subset of these transcripts appears to be expressed in the other tissues. In situ hybridization analysis of 14 and 18 day old mouse embryos indicates that trkB transcripts are localized in the central (CNS) and peripheral (PNS) nervous systems, including brain, spinal cord, spinal and cranial ganglia, paravertebral trunk of the sympathetic nervous system and various innervation pathways. These results suggest that trkB may code for a novel cell surface receptor involved in neurogenesis.

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

“…The anti‐trkB antibody recognized a protein band with a relative mw ≅ 140 kDa (Figure 2), consistent with the mw of the full‐length, biologically active form of the receptor protein (Klein, Parada, Coulier, & Barbacid, 1989). The relative levels of trkB receptor protein (RLA = 0.40 ± 0.05 vs. RHA = 0.68 ± 0.12) were 25% lower in the RLA versus the RHA line ( p  < .05; Table 1).…”

Specific neurotrophin binding to leucine‐rich motif peptides of TrkA and TrkB

“…The rat TrkA [22] and rat TrkB [23] sequences correspond to the ones of the L2A and L2B peptides used in this work. The sequences of human TrkA, mouse TrkB, and chick TrkB were taken from Martin-Zanca et al [19], Klein et al [12], and Dechant et al [3], respectively. The localizations of the motifs within the respective proteins are indicated by the numbers on either side of the sequences.…”

Pituitary adenylate cyclase-activating polypeptide is an autocrine inhibitor of mitosis in cultured cortical precursor cells

“…4e) and that elicited by IGF alone [IGF ϭ 100 Ϯ 4%, IGF ϩ PACAP ϭ 64 Ϯ 5%, (percentage control Ϯ SEM), P Ͻ 0.03] or bFGF alone (bFGF ϭ 100 Ϯ 3%, bFGF ϩ PACAP ϭ 72 Ϯ 2%, P Ͻ 0.007), suggesting that PACAP provides a general signal to induce cell cycle withdrawal. In contrast, the neurotrophins (NT3, BDNF, NGF) survival and differentiation factors expressed in developing cortex (7,8,(23)(24)(25)(26)(27) did not affect DNA synthesis (data not shown), suggesting that PACAP plays a distinct role (note: trophic activity was exhibited by NT3 and NGF in sympathetic, and BDNF in cerebellar granule, cultures).…”

“…Consequently, we characterized PACAP effects on biochemical and morphological markers of differentiation. BDNF and its trkB receptor are widely expressed in developing cortex (25)(26)(27), promoting differentiation and survival (8,23). Initially undetectable at E14, trkB expression in vivo increases progressively with de- velopment (24).…”