Differential Expression and Sequence-specific Interaction of Karyopherin α with Nuclear Localization Sequences

doi:10.1074/jbc.272.7.4310

Differential Expression and Sequence-specific Interaction of Karyopherin α with Nuclear Localization Sequences*

From the Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121

^‡ To whom correspondence should be addressed:
Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Ave., Seattle, WA 98121
. Tel.: 206-727-3543; Fax: 206-727-3600; E-mail: Steven_G._Nadler{at}ccmail.bms.com.

Abstract

The process of nuclear protein transport requires the interaction of several different proteins, either directly or indirectly with nuclear localization or targeting sequences (NLS). Recently, a number of karyopherins α, or NLS-binding proteins, have been identified. We have found that the karyopherins hSRP1 and hSRP1α are differentially expressed in various leukocyte cell lines and could be induced in normal human peripheral blood lymphocytes. We show that the two karyopherins bind with varied specificities in a sequence specific manner to different NLSs and that the sequence specificity is modulated by other cytosolic proteins. There was a correlation between binding of karyopherins α to different NLSs and their ability to be imported into the nucleus. Taken together, these data provide evidence for multiple levels of control of the nuclear import process.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

NLS

nuclear localization sequence

K1

hSRP1

K2

hSRP1α

BSA

bovine serum albumin

FITC

fluorescein isothiocyanate

ECL

electrochemiluminescent

PBS

phosphate-buffered saline

GST

glutathione S-transferase

PAGE

polyacrylamide gel electrophoresis.
↵² S. G. Nadler and J. S. Cleaveland, manuscript in preparation.
- Received November 6, 1996.
- Revision received December 5, 1996.