The Src family of tyrosine protein kinases in hemopoietic signal transduction

Bolen, Joseph B.; Rowley, Roy; Spana, Carl; Tsygankov, Alexander Y.

doi:10.1096/fasebj.6.15.1281458

Cited by 223 publications

(139 citation statements)

References 2 publications

(2 reference statements)

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“…Like other Src family kinases, Lck contains a C-terminal kinase domain, a single Src homology 2 (SH2) and SH3 domain, and an N-terminal region that is distinct from other family members (26). SH3 domains are able to mediate protein interactions by binding certain proline-rich amino acid sequences (27,28), and a number of proteins have been reported to bind the Lck SH3 domain including c-Cbl, PI-3-K, Ras-GAP, HS1, and CD2 (29 -33).…”

Section: Activation Of T-lymphocytes Is Initiated By Engagement Of Thmentioning

confidence: 99%

The Lck SH3 Domain Is Required for Activation of the Mitogen-activated Protein Kinase Pathway but Not the Initiation of T-cell Antigen Receptor Signaling

Denny

Kaufman

Chan

et al. 1999

Journal of Biological Chemistry

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Section: Activation Of T-lymphocytes Is Initiated By Engagement Of Thmentioning

confidence: 99%

The Lck SH3 Domain Is Required for Activation of the Mitogen-activated Protein Kinase Pathway but Not the Initiation of T-cell Antigen Receptor Signaling

Denny

Kaufman

Chan

et al. 1999

Journal of Biological Chemistry

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“…These enzymes have been implicated in signal-transduction pathways, and Lyn, which is expressed in a wide range of tissues and cell types, has been shown to physically and functionally associate with various receptor molecules and, therefore, to be localized at the cell membrane [37]. It has been suggested that, as a consequence of their localization, the Src family tyrosine kinases may be accessible to distinct regulatory proteins and substrates.…”

Section: Discusslonmentioning

confidence: 99%

Association of Lyn Tyrosine Kinase with the Nuclear Matrix and Cell‐Cycle‐Dependent Changes in Matrix‐Associated Tyrosine Kinase Activity

Radha

Nambirajan

Swarup

1996

European Journal of Biochemistry

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The nuclear matrix isolated from HeLa cells and Rat2 fibroblasts harbor? tyrosine kinase and tyrosine phosphatase activities. Polypeptides of 53, 56 and 60 kDa, associated with this subnuclear structure, were phosphorylated at tyrosine in vivo. By immunoblot and immunolabelling experiments, we identified one of the nuclear-matrix-associated tyrosine kinases as Lyn, a Src family member. Lyn was distributed as foci throughout the matrix. The p56 and p53 isoforms of Lyn remained firmly associated with the nuclear matrix after a variety of matrix preparation procedures, and were not detectable in the chromatin fraction of the nucleus. The tyrosine kinase activity associated with the nuclear matrix showed cell-cycle-dependent changes, maximum activity being observed at the G,/S transition phase. Polyoma-virus-transformed rat fibroblast cells showed sixfold higher tyrosine kinase activity in the nuclear matrix preparations compared to that in untransformed cells. These observations are consistent with the suggestion that tyrosine kinase activity associated with the nuclear matrix may be an important determinant of cellular proliferation.Keywords: nuclear matrix ; Lyn tyrosine kinase ; cell cycle ; protein phosphorylation ; nuclear tyrosine kinase.Phosphorylation at tyrosine residues regulates properties of proteins such as enzyme activity, subcellular localization and intermolecular interaction. In eukaryotic cells, this modification effects the response of the cell to its external environment by helping to transmit signals from the cell membrane across the cytoplasm to the nucleus, where actual control of gene expression takes place [I]. The intracellular protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) are either associated with various structures such as the plasma membrane, endoplasmic reticulum, cytoskeleton, spindle fibres and mitochondria or are present in a soluble form in the cytoplasm [2, 31. The activities and substrate specificities of these enzymes in vivo are determined by phosphorylation, association with other proteins and subcellular compartmentalization [4, 51.Recent studies have identified the presence of tyrosine-phosphorylated proteins in the nucleus and their role in cell-cycle control and as transcription factors [6, 71. Both cytoplasmic and nuclear proteins are phosphorylated at tyrosine residues in the signalling pathway of mitogenesis. A few tyrosine kinases and phosphatases have been shown to localize to the nucleus, but their physiological functions have not been well defined 13, 81. PTKs known to localize to the nucleus constitutively are Wee 1, Abl, Fer/Fer T and Fgr 181. The Src tyrosine kinase, which is the prototype member of the Src family of kinases, is an ubiqui- tously expressed cytoplasmic enzyme and has been shown to be localized in the nucleus of calcium-induced differentiating keratinocytes 191. Studies on the subnuclear distribution of the tyrosine phosphorylated proteins and the PTKs and PTPs are generally lacking and could provide clues to the role of...

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“…The Src family consists of nine related protein tyrosine kinases that participate in signaling from cell surface receptors to the interior of the cell (reviewed in Cantley et al, 1991;Bolen et al, 1992). All members of the Src family are covalently modified by the 14-carbon fatty acid myristate.…”

Section: Introductionmentioning

confidence: 99%

Palmitoylation of p59fyn is reversible and sufficient for plasma membrane association.

Wolven

Okamura

Rosenblatt

et al. 1997

MBoC

160

155

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Members of the Src family of protein tyrosine kinases are localized to subspecialized regions of the plasma membrane. Herein we show that the N-terminal SH4 region of the Src family member p59tf-" (Fyn) is both necessary and sufficient for targeting of Fyn and heterologous proteins to the plasma membrane and detergent-insoluble subdomains. Attachment of the first 16 amino acids of Fyn to a normally cytosolic protein, ,B-galactosidase, resulted in distinct plasma membrane localization of the chimeric protein.Mutation of the palmitoylation site (cysteine-3) within Fynl6-43-galactosidase or wildtype Fyn abrogated plasma membrane localization, resulting in redistribution of the mutant proteins into intracellular membranes. Substitution of the SH4 motif within Fyn with heterologous sequences from other palmitoylated proteins (Gao and GAP43) revealed that the presence of palmitate is sufficient to direct plasma membrane localization independent of surrounding amino acid sequences and myristate. Palmitoylated Fyn chimeras were also enriched in the Triton X-100-resistant matrix, whereas nonpalmitoylated forms of these proteins were detected in the detergent-soluble fraction. The palmitate moiety on Fyn exhibited a half-life of 1.5-2 h. In contrast, the half-life of the polypeptide backbone was 8 h, indicating that palmitoylation is a reversible modification. These studies establish that the palmitoylated SH4 sequence of Fyn can be used to specifically target proteins to the plasma membrane in a reversible manner.

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The Src family of tyrosine protein kinases in hemopoietic signal transduction

Cited by 223 publications

References 2 publications

The Lck SH3 Domain Is Required for Activation of the Mitogen-activated Protein Kinase Pathway but Not the Initiation of T-cell Antigen Receptor Signaling

The Lck SH3 Domain Is Required for Activation of the Mitogen-activated Protein Kinase Pathway but Not the Initiation of T-cell Antigen Receptor Signaling

Association of Lyn Tyrosine Kinase with the Nuclear Matrix and Cell‐Cycle‐Dependent Changes in Matrix‐Associated Tyrosine Kinase Activity

Palmitoylation of p59fyn is reversible and sufficient for plasma membrane association.

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