Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity.

Golden, Andy; Nemeth, S P; Brugge, Joan S.

doi:10.1073/pnas.83.4.852

Cited by 310 publications

(146 citation statements)

References 45 publications

(23 reference statements)

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…For example, postmitotic differentiated or differentiating neurons express high levels of both c-src proteins (1,3,7,8,17,21). Mammalian platelets, terminally differentiated cells with no growth potential, express still higher levels of the smaller c-src protein (9). These observations suggest that tyrosine-specific protein kinases in general, and pp60c-sr in particular, may regulate cellular processes that are distinct from growth control.…”

mentioning

confidence: 71%

Platelet tyrosine-specific protein phosphorylation is regulated by thrombin.

Ferrell¹,

Martin²

1988

Mol. Cell. Biol.

230

120

View full text Add to dashboard Cite

Intact human platelets, terminally differentiated cells with no growth potential, were found to possess unusually high levels of tyrosine-specific protein phosphorylation. The physiological platelet activator thrombin transiently elevated platelet phosphotyrosine content, apparently through stimulation of one or more tyrosine-specific protein kinases. Immunoblotting with antiphosphotyrosine antiserum showed that thrombin caused dramatic changes in the tyrosine phosphorylation of a number of individual protein bands and that these changes occurred in three distinct temporal waves. Most but not all of the protein bands phosphorylated at tyrosine in response to thrombin were also tyrosine phosphorylated in response to chilling or the combination of ionophore A23187 and tetradecanoylphorbol acetate. Thrombin stimulated the phosphorylation of the tyrosine kinase pp6OC-S', primarily at Ser-12 and Tyr-527, although the effects of these phosphorylations on platelet pp60csrC function were not apparent. Together, these results suggest that tyrosine-specific protein kinases of uncertain identity are involved in signal transduction in platelets.The phosphorylation of proteins at tyrosine residues is implicated in normal and abnormal cell growth: several growth factor receptors are tyrosine-specific protein kinases, as are the transforming proteins of one class of acutely oncogenic retroviruses (13). The best-studied such retrovirus is Rous sarcoma virus, whose transforming gene v-src was derived from a cellular tyrosine kinase gene, c-src (22, 23). The protein-tyrosine kinase activity of the v-src gene product pp60vsrc has been activated by a C-terminal substitution and scattered point mutations (12). The transforming capacity of pp60v-src results, at least in part, from its increased kinase activity.Through alternative splicing, the c-src gene gives rise to two distinct proteins, both of about 60 kilodaltons (kDa) (16,18). Little is known about the physiological function of either c-src protein. A number of other proto-oncogene products are involved in the transduction of normal mitogenic signals (e.g., c-erbB [epidermal growth factor receptor], c-fms [colony-stimulating factor 1 receptor], c-sis [platelet-derived growth factor]). However, the tissue distribution of pp6Oc-src expression suggests that this is not its function; those cells which express the highest levels of pp60csrc do not divide. For example, postmitotic differentiated or differentiating neurons express high levels of both c-src proteins (1,3,7,8,17,21). Mammalian platelets, terminally differentiated cells with no growth potential, express still higher levels of the smaller c-src protein (9). These observations suggest that tyrosine-specific protein kinases in general, and pp60c-sr in particular, may regulate cellular processes that are distinct from growth control.We have chosen human platelets as a system for investigating the role of protein-tyrosine phosphorylation in differentiated cells. Platelets are relatively simple cell fragments (they do not syn...

show abstract

mentioning

confidence: 71%

Platelet tyrosine-specific protein phosphorylation is regulated by thrombin.

Ferrell¹,

Martin²

1988

Mol. Cell. Biol.

230

120

View full text Add to dashboard Cite

show abstract

“…This kinase plays an important role in the control of cell division [3], cell growth and differentiation [4] and has a distinctive function in bone formation [5]. Significant amounts of pp60 c_src are present in blood platelets [6] and neurons [7] suggesting that the role of pp60 c-src is not only restricted to growth and differentiation of proliferating cells but may display other functions.…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylinositol 4,5‐bisphosphate specifically stimulates PP60^c‐src catalyzed phosphorylation of gelsolin and related actin‐binding proteins

Corte¹,

Gettemans²,

Vandekerckhove³

1997

FEBS Letters

View full text Add to dashboard Cite

Gelsolin is a widely distributed Ca -dependent regulator of the cortical actin network. We demonstrate that gelsolin is phosphorylated by pp60 c~src and that this phosphorylation is dramatically enhanced by phosphatidylinositol 4,5-bisphosphate (PIP 2 ), known to specifically interact with gelsolin. Other phospholipids display only a marginal effect. pp56 lck , a tyrosine kinase of the same family, does not phosphorylate gelsolin. Other mammalian actin-binding proteins such as profilin and CapG but also fragmin from Physamm polycephalum are similar targets for PIP 2 -stimulated pp60 c " src phosphorylation.

show abstract

“…The binding of full length c-Src with p58 gag was demonstrated by incubating platelet lysates, which contain a high level of Src (Golden et al, 1986), with in vitro-translated, labeled p58 gag (Juang et al, 1994) and immunoprecipitating with anti-Src or nonimmune serum (Figure 2). Since MAT-C1 microvillar p58 gag is constitutively phosphorylated on tyrosine (Juang et al, 1996), the binding and phosphorylation of p58 gag by Src were examined using a GST fusion protein of p58 gag .…”

Section: Binding Of P58 Gag To Recombinant Sh3 Domain Of Srcmentioning

confidence: 99%

c-Src association with and phosphorylation of p58gag, a membrane- and microfilament-associated retroviral Gag-like protein in a xenotransplantable rat mammary tumor

Huang

Zhang

et al. 1999

Oncogene

View full text Add to dashboard Cite

The retroviral Gag-like protein p58 gag expressed in a highly metastatic ascites rat mammary adenocarcinoma has been implicated in cell surface changes contributing to xenotransplantability. p58 gag is present in the cells in a plasma membrane-and micro®lament-associated signal transduction particle containing Src and is phosphorylated on tyrosine. Overlay analyses and a nity chromatography with glutathione S-transferase (GST) fusion proteins of Src homology-3 (SH3) domains showed direct binding of the Src but not the Crk SH3 domain to p58 gag . This association was con®rmed by coimmunoprecipitation of partially puri®ed p58 gag from ascites cell lysates with platelet Src. Further, a GSTp58 gag fusion protein bound full length c-Src from either platelets or c-Src-expressing insect cells. The GST-p58 gag fusion protein, but not GST, was phosphorylated by platelet or insect cell-expressed c-Src, but not by a kinase negative c-Src variant. The binding of GST-p58 gag to c-Src was almost completely abolished by a 50-fold excess of the GST-SH3 domain of Src, and a parallel decrease in tyrosine phosphorylation of p58 gag was observed. These results demonstrate that p58 gag is tyrosine-phosphorylated as a consequence of its speci®c association with c-Src via its SH3 domain. These observations suggest a mechanism by which Gag proteins may contribute to retroviral maturation or pathogenesis through binding and relocalization of SH3 domaincontaining proteins such as Src-like tyrosine kinases to sites of association of micro®laments with the plasma membrane.

show abstract

Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity.

Cited by 310 publications

References 45 publications

Platelet tyrosine-specific protein phosphorylation is regulated by thrombin.

Platelet tyrosine-specific protein phosphorylation is regulated by thrombin.

Phosphatidylinositol 4,5‐bisphosphate specifically stimulates PP60^c‐src catalyzed phosphorylation of gelsolin and related actin‐binding proteins

c-Src association with and phosphorylation of p58gag, a membrane- and microfilament-associated retroviral Gag-like protein in a xenotransplantable rat mammary tumor

Contact Info

Product

Resources

About

Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity.

Cited by 310 publications

References 45 publications

Platelet tyrosine-specific protein phosphorylation is regulated by thrombin.

Platelet tyrosine-specific protein phosphorylation is regulated by thrombin.

Phosphatidylinositol 4,5‐bisphosphate specifically stimulates PP60c‐src catalyzed phosphorylation of gelsolin and related actin‐binding proteins

c-Src association with and phosphorylation of p58gag, a membrane- and microfilament-associated retroviral Gag-like protein in a xenotransplantable rat mammary tumor

Contact Info

Product

Resources

About

Phosphatidylinositol 4,5‐bisphosphate specifically stimulates PP60^c‐src catalyzed phosphorylation of gelsolin and related actin‐binding proteins