BOTH THE SH2 AND SH3 DOMAINS OF HUMAN CRK PROTEIN ARE REQUIRED FOR NEURONAL DIFFERENTIATION OF PC12 CELLS

被引:107
作者
TANAKA, S
HATTORI, S
KURATA, T
NAGASHIMA, K
FUKUI, Y
NAKAMURA, S
MATSUDA, M
机构
[1] NATL INST HLTH,DEPT PATHOL,1-23-1 TOYAMA,SHINJUKU KU,TOKYO 162,JAPAN
[2] NATL INST NEUROSCI,NCNP,DIV BIOCHEM & CELLULAR BIOL,KODAIRA,TOKYO 187,JAPAN
[3] RES DEV CORP JAPAN,PRESTO,KYOTO 61902,JAPAN
[4] UNIV TOKYO,FAC AGR,BIOCHEM LAB,BUNKYO KU,TOKYO 113,JAPAN
[5] HOKKAIDO UNIV,SCH MED,DEPT PATHOL,KITA KU,SAPPORO,HOKKAIDO 060,JAPAN
关键词
D O I
10.1128/MCB.13.7.4409
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human CRK protein is a homolog of the chicken v-crk oncogene product and consists mostly of src homology region 2 (SH2) and SH3, which are shared by many proteins, in particular those involved in signal transduction. SH2 has been shown to bind specifically to phosphotyrosine-containing peptides. We report here that both SH2 and SH3 are required for signaling from CRK protein. Microinjection of the CRK protein induced neurite formation of rat pheochromocytoma cell line PC12. This activity was abolished by mutation of the CRK protein in either SH2 or SH3. The neuronal differentiation induced by the CRK protein was blocked by an excess amount of peptides containing CRK SH3. Moreover, we identified three proteins, of 118, 125, and 136 kDa, which bound specifically to CRK SH3. The CRK-induced neuronal differentiation was also suppressed by monoclonal antibodies against either CRK SH2 or p21ras. These results suggest that both SH2 and SH3 of the CRK protein mediate specific protein-protein binding and that the resulting multimolecular complex generates a signal for neurite differentiation through activation of p21ras.
引用
收藏
页码:4409 / 4415
页数:7
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