calmodulin-dependent protein kinase kinases in the adult rat brain

S.122

TYROSINE PHOSPHORYLATION NEUROTROPHINS

183 HIROSHI

OHNISHI’,

MASASHI

Minamiooya,

expressed

molecule

with tyrosine-based

activation

Previously

Furthermore,

2 signaling

brain-derived

neurotrophic

as NGF, BDNF and NT-3.

ENHANCED ABNORMAL

Laboratory

KOJIMA,

Previous

investigations

synaptic

transmission

Extracellular

mechanism

(BDNF)

have suggested and synaptic we observed

ISHIBASHI,

hyperphosphorylation

results showed an abnormal

HIROWKI

excitability.

fear response

kinase may modulate complex behavioral

185

(NT-j)

responses,

to neurotrophic

activity.

tyrosine

factor\ such

So BIT-SHP-2

SUBUNIT

SIMONE STORK, KUNIHIKO

Sciences,

pathway

2B AND

OBATA

Okazaki, Aichi 4444585 tyrosine

kinases,

plays an important mice overexpressing

by Fyn. In vitro kinase experiments intracellular

role in Fyn in

To investigate

possible

implications

we studied a variety of behavioral in these animals.

showed that Fyn was

domain of the NR2B. The finding

Our observation

of the NR2B may also of enhanced

protein

traits in fyn-transgenic

mice.

thus suggests

that Fyn tyrosine

such as emotional behavior.

OF TWO ISOFORMS OF Ca* +/CALMODULIN-DEPENDENT KINASES IN THE ADULT RAT BRAIN

, TAKAKO

induced

Our results suggest that the BIT-SHP-

EXPRESSION

SAKAGAMI'

also

kindling suggests that altered phosphorylation

by Fyn on animal behavior,

and this

of the NMDA receptor subunit 2B (NR2B) in these mice and,

phophorylated

the NMDA receptor activity and neuronal phosphorylation

cytoplusmic

SHP-2,

complex formation between BIT and

In the course of studies using the transgenic

mice exhibited an accelerated

is

signal and intercellular association.

that Fyn, a member of non-receptor

plasticity.

which

In this study, we found that nerve growth factor

or neurotrophin-3

able to phosphorylate multiple tyrosine residues in the carboxyl-terminal

Preliminary

Inst. for

glycoprotein

phosphatase

of neurons which acts in response

National Institute for Physiological

found that the NR2B is preferentially

that fyn-overexpressing

tyrosine

BY

SANO’

that tyrosine-phosphorylated

protein tyrosine

domain of BIT has neural cell recognition

OLIVER STORK, HIDETOSHI

neurons of the forebrain,

modulate

INDUCED

and SHIN-ICHIRO

TYROSINE PHOSPHORYLATION OF THE NMDA RECEPTOR EMOTIONAL RESPONSE IN FYN-TRANSGENIC MICE.

of Neurochemistry,

forthermore,

we reported

of BIT and subsequent

factor

may be important for the cross-talk between neurotrophin

NOBUHIKO

SHP-2

is a membrane

of BIT and association with SHP-2 in primary cultured rat neurons.

pathway is a novel signal transduction

184

motifs)

activity of SHP-2.

(NGF) treatment of PC12 cells leads to tyrosine phosphorylation

phosphorylation

WITH

HIROSHI HATANAKA’.

2 (SH2) domain-containing

results in potent stimulation of phosphatase

SHP-2.

BIT

Machida, Tokyo 194-851 I, ‘Division of Protein Biosynthesis,

in the brain at the adult stage.

domain of BIT interacts with the Src homology association

OF

Osaka Univ., Yamadaoka, Suita, Osaka 5650871

BIT (brain jmmunoglobulin-like dominantly

ASSOCIATION

YAMADA’, MISAE KUBOTA’,

‘Mitsubishi Kasei Inst. of Life Sciences, Protein Research,

AND

KITANI*,

SACHIKO

KONDOl 1 Div. of Histology, Dept. of Cell Biology, Graduate Aoba-ku, Sendai 980-8575, * Dept. of Biochemistry, Asahikawa 078-8307.

OKUNO*, HITOSHI

PROTEIN

FUJISAWA*,

KINASE

HISATAKE

School of Medical Sciences, Tohoku Univ.. Asahikawa Medical College, Nishikagura,

in regulating the (CaMKK) is thought to be involved kinase I and IV. We have used in situ hybridization protein of the mRNA for two isoforms (a and !$) of CaMKKs in the adult rat CaMKKP mRNAs were distributed brain. CaMKKa mRNAs were distributed widely throughout the neuroaxis, for CaMKKa mRNAs was detected in the in relatively restricted neuronal populations. Highest expression hippocampal formation, moderate expression in the olfactory bulb, cerebral cortex, thalamic nuclei, brain cerebellar granule cells and Purkinje and spinal cord; and weak expression in the striatum, stem nuclei, detected in the cerebellar granule cells, moderate cells. Highest expression for CaMKKP mRNAs was weak expression in the striatum, pontine nuclei, spinal expression in the olfactory bulb and cerebral cortex; cord. We have also used immunohistochemistry to and dorsal horn of the spinal trigeminal nuclei, CaMKKa by raising monoclonal antibodies. CaMKKadetermine the subcellular localization of immunoreactivity was localized in the neuronal, cytoplasm and dendrite, but not in the nucleus. These findings suggest that two isoforms of CaMKKS may be involved in different roles in the Caz+-signaling.

Ca2+/calmodulin-dependent activities of histochemistry

protein

kinase

both Caz+/calmodulin-dependent to examine the distribution

kinase