Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain

2005 ◽  
Vol 490 (2) ◽  
pp. 119-132 ◽  
Author(s):  
Jesús Mariano Ureña ◽  
Anna La Torre ◽  
Albert Martínez ◽  
Eve Lowenstein ◽  
Neus Franco ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Developmental Regulation ◽  
Adult Brain ◽  
Synaptic Localization

scholarly journals Insulin and insulinlike growth factor 1 (IGF-1) receptors during central nervous system development: expression of two immunologically distinct IGF-1 receptor beta subunits.

1989 ◽  
Vol 9 (7) ◽  
pp. 2806-2817 ◽  
Author(s):  
R S Garofalo ◽  
O M Rosen
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
System Development ◽  
Fetal Brain ◽  
Nervous System Development ◽  
Adult Brain ◽  
Beta Subunit ◽  
Tyrosine Kinase Domain ◽  
Beta Subunits ◽  
Insulinlike Growth Factor

Insulin and insulinlike growth factor 1 (IGF-1) receptors are present in brain, yet their function remains obscure. Expression of these tyrosine kinase-bearing growth factor receptors during rat brain development was examined by using three antipeptide antibodies directed against epitopes in the beta subunits (AbP2, AbP4, and AbP5). All three antibodies recognized both insulin and IGF-1 receptors. Membranes were prepared from fetal brains (14 to 21 days of gestation), neonatal brain (postnatal day 1), and adult brain. Immunoblot analyses using AbP4 and AbP5 revealed a 92-kilodalton (kDa) protein that corresponded to the beta subunit of the insulin and IGF-1 receptors. Densitometric scanning of immunoblots indicated that receptor proteins were 4- to 10-fold more abundant in fetal brain membranes than in membranes from adult brain. Expression was highest during 16 to 18 days of gestation and declined thereafter to the relatively low level found in adult brain. Immunoblot analyses with AbP2 as well as ligand-activated receptor autophosphorylation revealed an additional protein of 97 kDa. This protein was phosphorylated in response to IGF-1 and was not directly recognized by AbP4 or AbP5. The covalent association of the 97-kDa protein with the 92-kDa beta subunit was indicated by the ability of AbP4 and AbP5 to immunoprecipitate both proteins under nonreducing conditions but only the 92-kDa protein after reduction. In contrast, AbP2 immunoprecipitated both proteins regardless of their association. This immunospecificity remained unchanged after deglycosylation of the isolated proteins. Two-dimensional tryptic phosphopeptide analysis showed that the 92- and 97-kDa subunits of the IGF-1 receptor are related but distinct proteins. Taken together, the data suggest that the 92- and 97-kDa subunits differ in primary amino acid sequence. Thus, two distinct beta subunits may be present in a single IGF-1 receptor in brain. These subunits have in common an epitope recognized by an antibody to the tyrosine kinase domain (AbP2) but differ in regions thought to be important in receptor kinase regulation and signal transduction.

scholarly journals Expansion of RNA sequence diversity and RNA editing rates throughout human cortical development

2021 ◽  
Author(s):  
Ryn Cuddleston ◽  
Laura Sloofman ◽  
Lindsay Liang ◽  
Enrico Mossotto ◽  
Xuanjia Fan ◽  
...  
Keyword(s):  
Rna Editing ◽  
Developmental Regulation ◽  
Cortical Development ◽  
Sequence Diversity ◽  
Adult Brain ◽  
Murine Models ◽  
Human Cortex ◽  
Hyperactivity Disorder ◽  
The Brain ◽  
Human Primate

Post-transcriptional modifications by RNA editing are essential for neurodevelopment, yet their developmental and regulatory features remain poorly resolved. We constructed a full temporal view of base-specific RNA editing in the developing human cortex, from early progenitors through fully mature cells found in the adult brain. Developmental regulation of RNA editing is characterized by an increase in editing rates for more than 10,000 selective editing sites, shifting between mid-fetal development and infancy, and a massive expansion of RNA hyper-editing sites that amass in the cortex through postnatal development into advanced age. These sites occur disproportionally in 3-UTRs of essential neurodevelopmental genes. These profiles are preserved in non-human primate and murine models, illustrating evolutionary conserved regulation of RNA editing in mammalian cortical development. RNA editing levels are commonly genetically regulated (editing quantitative trait loci, edQTLs) consistently across development or predominantly during prenatal or postnatal periods. Both consistent and temporal-predominant edQTLs co-localize with risk loci associated with neurological traits and disorders, including attention deficit hyperactivity disorder, schizophrenia, and sleep disorders. These findings expand the repertoire of highly regulated RNA editing sites in the brain and provide insights of how epitranscriptional sequence diversity by RNA editing contributes to neurodevelopment.

scholarly journals Structure and developmental regulation of the B-lymphoid tyrosine kinase gene blk.

1992 ◽  
Vol 267 (7) ◽  
pp. 4815-4823 ◽  
Author(s):  
S.M. Dymecki ◽  
P Zwollo ◽  
K Zeller ◽  
F.P. Kuhajda ◽  
S.V. Desiderio
Keyword(s):  
Tyrosine Kinase ◽  
Developmental Regulation ◽  
Kinase Gene ◽  
Tyrosine Kinase Gene ◽  
B Lymphoid
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