SH3 domains direct cellular localization of signaling molecules

Bar–Sagi, Dafna; Rotin, Daniela; Batzer, A.; Mandiyan, Valsan; Schlessinger, Joseph

doi:10.1016/0092-8674(93)90296-3

Cited by 336 publications

(177 citation statements)

References 39 publications

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“…Examining the sequence of KHS reveals three PXXP motifs, two of which ®t the class II polyproline helix structure (Cohen et al, 1995;Yu et al, 1994). Proteins containing these consensi are predicted to bind SH3-containing proteins and have proven to be regulatory for localization or activity (Bar-Sagi et al, 1993). Other proteins which contain this motif include the GTPase dynamin (Gout et al, 1993), the Rho-GAP 3BP-1 (Cicchetti et al, 1992(Cicchetti et al, , 1995Ren et al, 1993), and the guanine nucleotide exchange factor Sos1 .…”

Section: Discussionmentioning

confidence: 99%

A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase

Tung

Blenis

1997

Oncogene

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STE20-homologous proteins have been implicated in mammalian MAP kinase pathways as important transducers of signals from p21 family GTPases. We have cloned a novel STE20 family member, which we call KHS for kinase homologous to SPS1/STE20, that encodes a kinase of 95 kD which is expressed in a variety of tissues. Transiently expressed fusion protein GST-KHS exhibits phosphotransferase activity toward a panel of test substrates, including myelin basic protein (MBP), which is phosphorylated by all known STE20 homologues. KHS is most closely related to another human STE20, GC kinase (74% similar in the catalytic domain), which has recently been placed upstream of the stress-activated MAP kinases (SAPKs/JNKs. KHS also activates JNK in transient coexpression experiments, suggesting a role for KHS in the stress response of ®broblasts. Characterization and comparison of the regulation of these two kinases will be important in elucidating MAP kinase signalling cascades.

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Section: Discussionmentioning

confidence: 99%

A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase

Tung

Blenis

1997

Oncogene

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“…The specimens were dried by incubation at 378C for 45 min and mounted for microscopy in a solution containing 80% glycerol and 2.5% Dabco in PBS. The extraction bu er used to examine cytoskeleton integrity was as described (Bar-Sagi et al, 1993). Control experiments demonstrated negligible staining with secondary antibodies alone.…”

Section: Immuno¯uorescencementioning

confidence: 99%

At the onset of transformation polyomavirus middle-T recruits shc and src to a perinuclear compartment coincident with condensation of endosomes

et al. 1998

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To examine the early cellular changes that accompany transformation, middle-T antigen (the transforming protein of polyomavirus), was expressed from an inducible promoter in Rat2 ®broblasts and in normal diploid human ®broblast (MRC5) cells using a replication defective adenovirus vector. The earliest detectable expression of middle-T antigen correlated closely with the initial changes in cellular morphology. At this time, expression of middle-T antigen resulted in the redistribution of shc and src to a brefeldin A resistant perinuclear compartment coincident with the formation of kinase active complexes containing middle-T antigen, shc and src. The ®rst detectable changes directly related to altered morphology was reorgnization of actin ®laments, and the condensation of tubular endosomes in the perinuclear region of the cell. These results suggest a potential role for perinuclear localized mT molecules in some of the morphologic changes associated with the initial phase of cellular transformation.

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“…Several investigators have demonstrated transforming capacity of both full length PLC-g and the isolated SH2-SH2-SH3 moiety (Bar-Sagi et al, 1993;Chang et al, 1997;Schlessinger, 1994;Smith et al, 1998). Its link to calcium homeostasis, transmembrane signal transduction, and transforming potential made it a putative target protein in the calcium in¯ux stress model.…”

Section: Introductionmentioning

confidence: 99%