scholarly journals A cytosolic activity distinct from Crm1 mediates nuclear export of protein kinase inhibitor in permeabilized cells

1998 ◽  
Vol 95 (25) ◽  
pp. 14739-14744 ◽  
Author(s):  
J. M. Holaska ◽  
B. M. Paschal
Keyword(s):  
Protein Kinase ◽  
Nuclear Export ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Permeabilized Cells

Cloning and mapping of human PKIB and PKIG, and comparison of tissue expression patterns of three members of the protein kinase inhibitor family, including PKIA

2000 ◽  
Vol 349 (2) ◽  
pp. 403-407 ◽  
Author(s):  
Lihua ZHENG ◽  
Long YU ◽  
Qiang TU ◽  
Min ZHANG ◽  
Hua HE ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Nuclear Export ◽  
Kinase Inhibitor ◽  
Expression Patterns ◽  
Nuclear Export Signal ◽  
Tissue Expression ◽  
Protein Kinase Inhibitor ◽  
The Other ◽  
Dependent Protein

Two novel members of the human cAMP-dependent protein kinase inhibitor (PKI) gene family, PKIB and PKIG, were cloned. The deduced proteins showed 70% and 90% identity with mouse PKIβ and PKIγ respectively. Both the already identified pseudosubstrate site and leucine-rich nuclear export signal motifs were defined from the 11 PKIs of different species. The PKIB and PKIG genes were mapped respectively to chromosome 6q21-22.1, using a radiation hybrid GB4 panel, and to chromosome 20q13.12-13.13, using a Stanford G3 panel. Northern-blot analysis of three PKI isoforms, including the PKIA identified previously, revealed significant differences in their expression patterns. PKIB had two transcripts of 1.9 kb and 1.4 kb. The former transcript was abundant in both placenta and brain and the latter was expressed most abundantly in placenta, highly in brain, heart, liver, pancreas, moderately in kidney, skeletal muscle and colon, and very little in the other eight tissues tested. PKIG was widely expressed as a 1.5-kb transcript with the highest level in heart, hardly detectable in thymus and peripheral blood leucocytes and was moderately expressed in the other tissues, with slightly different levels. However, PKIA was specifically expressed as two transcripts of 3.3 kb and 1.5 kb in heart and skeletal muscle. The distinct expression patterns of the three PKIs suggest that their roles in various tissues are probably different.

Ca2+ is essential for multistep activation of the heat shock factor in permeabilized cells

1991 ◽  
Vol 11 (6) ◽  
pp. 3365-3368
Author(s):  
B D Price ◽  
S K Calderwood
Keyword(s):  
Heat Shock ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Heat Shock Factor ◽  
Cell System ◽  
Protein Kinase Inhibitor ◽  
Second Step ◽  
Hsp70 Gene ◽  
Permeabilized Cell ◽  
Permeabilized Cells

We have developed a novel permeabilized-cell system to study transcription mechanisms. In permeabilized cells, heat-induced activation of the heat shock factor and transcription of the hsp70 gene require Ca2+. Activation involves at least two steps: Ca(2+)- and heat-dependent activation of heat shock factor binding and a second step, prior to transcription of hsp70, that requires ATP and is sensitive to genistein, a protein kinase inhibitor.

scholarly journals Ca2+ is essential for multistep activation of the heat shock factor in permeabilized cells.

1991 ◽  
Vol 11 (6) ◽  
pp. 3365-3368 ◽  
Author(s):  
B D Price ◽  
S K Calderwood
Keyword(s):  
Heat Shock ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Heat Shock Factor ◽  
Cell System ◽  
Protein Kinase Inhibitor ◽  
Second Step ◽  
Hsp70 Gene ◽  
Permeabilized Cell ◽  
Permeabilized Cells

We have developed a novel permeabilized-cell system to study transcription mechanisms. In permeabilized cells, heat-induced activation of the heat shock factor and transcription of the hsp70 gene require Ca2+. Activation involves at least two steps: Ca(2+)- and heat-dependent activation of heat shock factor binding and a second step, prior to transcription of hsp70, that requires ATP and is sensitive to genistein, a protein kinase inhibitor.

scholarly journals Reproductive Function in Protein Kinase Inhibitor-Deficient Mice

2001 ◽  
Vol 21 (12) ◽  
pp. 3959-3963 ◽  
Author(s):  
Mouna Belyamani ◽  
Esha A. Gangolli ◽  
Rejean L. Idzerda
Keyword(s):  
Protein Kinase ◽  
Knockout Mice ◽  
Nuclear Export ◽  
Kinase Inhibitor ◽  
Physiological Role ◽  
Reproductive Function ◽  
Protein Kinase Inhibitor ◽  
Double Knockout ◽  
Genes Encoding ◽  
And Function

ABSTRACT The protein kinase inhibitor (PKI) family includes three genes encoding small, heat-stable inhibitors of the cyclic AMP-dependent kinase PKA. Each PKI isoform contains a PKA inhibitory domain and a nuclear export domain, enabling PKI to both inhibit PKA and remove it from the nucleus. The PKIβ isoform, also known as testis PKI, is highly expressed in germ cells of the testis and is found at more modest levels in other tissues. In order to investigate its physiological role, we have generated PKIβ knockout mice by gene targeting. These mice exhibit a partial loss of PKI activity in testis but remain fertile with normal testis development and function. PKIβ knockout females also reproduce normally. The PKIβ mutants were crossed with our previously derived PKIα mutants to obtain double-knockout mice. Remarkably, these mice are also viable and fertile with no obvious physiological defects in either males or females.

scholarly journals Multi-state recognition pathway of the intrinsically disordered protein kinase inhibitor by protein kinase A

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Cristina Olivieri ◽  
Yingjie Wang ◽  
Geoffrey C Li ◽  
Manu V S ◽  
Jonggul Kim ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Nuclear Export ◽  
Kinase Inhibitor ◽  
Intrinsically Disordered Protein ◽  
Protein Kinase Inhibitor ◽  
State Recognition ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Kinase A

In the nucleus, the spatiotemporal regulation of the catalytic subunit of cAMP-dependent protein kinase A (PKA-C) is orchestrated by an intrinsically disordered protein kinase inhibitor, PKI, which recruits the CRM1/RanGTP nuclear exporting complex. How the PKA-C/PKI complex assembles and recognizes CRM1/RanGTP is not well understood. Using NMR, SAXS, fluorescence, metadynamics, and Markov model analysis, we determined the multi-state recognition pathway for PKI. After a fast binding step in which PKA-C selects PKI’s most competent conformations, PKI folds upon binding through a slow conformational rearrangement within the enzyme’s binding pocket. The high-affinity and pseudo-substrate regions of PKI become more structured and the transient interactions with the kinase augment the helical content of the nuclear export sequence, which is then poised to recruit the CRM1/RanGTP complex for nuclear translocation. The multistate binding mechanism featured by PKA-C/PKI complex represents a paradigm on how disordered, ancillary proteins (or protein domains) are able to operate multiple functions such as inhibiting the kinase while recruiting other regulatory proteins for nuclear export.

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